Testing for particulates

ABSTRACT

A testing device (20, 120, 220, 290, 320, 420, 520, 620, 720, 820, 1020, 1120) is provided for testing for the presence of particulate in a liquid (22). The testing device (20, 120, 220, 290, 320, 420, 520, 620, 720, 820, 1020, 1120) includes a liquid container (30, 730) for containing the liquid (22); a filter (32, 132, 732), disposed in or downstream of the liquid container (30, 730); a liquid-pressure source (34, 734), which is arranged to apply pressure to drive the liquid (22) contained in the liquid container (30, 730) through the filter (32, 132, 732); and a filter chamber (36, 136, 236, 336, 736) that is (a) disposed downstream of the liquid container (30, 730), (b) shaped so as to define an inlet (38, 138, 238, 738, 838), and (c) in fluid communication with the filter (32, 132, 732). Other embodiments are also described.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application claims priority from U.S. ProvisionalApplication 62/727,268, filed Sep. 5, 2018, which is assigned to theassignee of the present application and incorporated herein byreference.

FIELD OF THE APPLICATION

Applications of the present invention relate to testing for the presenceof particulates, such as bacteria, in fluids.

BACKGROUND OF THE APPLICATION

Streptococcal pharyngitis, streptococcal tonsillitis, or streptococcalsore throat (known colloquially as strep throat) is a type ofpharyngitis caused by group A beta hemolytic streptococcus bacteria.Common symptoms include fever, sore throat, and enlarged cervical lymphnodes.

The rapid strep test is commonly used to test for the presence of groupA streptococcus bacteria. In this test, a swab is streaked across thethroat to collect bacteria, and is subsequently inserted into anextraction solution, e.g., a mixture of 2M sodium nitrite (hereinbelow,“solution A”), and 0.2M acetic acid (hereinbelow, “solution B”).(Hereinbelow, this mixture is sometimes referred to as “A and Bsolution.”) The extraction solution extracts strep A carbohydrateantigen from the bacteria. A dipstick containing an antibody specific tostrep A carbohydrate antigen is inserted into the mixture containing theantigen. The mixture migrates up the dipstick and reacts with theantibody, thus generating a line on the dipstick. The presence of thisline indicates a positive test result.

Other clinical situations also call for testing for presence of aparticulate. For example, a physician may wish to test a patient's bloodfor the presence of a virus, or a stool specimen for the presence of apathogen.

SUMMARY OF THE APPLICATION

In some applications of the present invention, a testing device isprovided for testing for presence of particulate in a liquid, such asgroup A streptococcus bacteria. The testing device typically comprises aliquid container for containing the liquid; a filter, disposed in ordownstream of the liquid container; and a liquid-pressure source, suchas a plunger, which is arranged to apply pressure to drive the liquidcontained in the liquid container through the filter. For someapplications, the liquid comprises gargled fluid, i.e., a gargle fluidthat the patient has gargled in his or her mouth and spit out, perhapsalong with some saliva. Alternatively, for some applications, the liquidcomprises saliva not swabbed from the throat of a patient.

There is therefore provided, in accordance with an Inventive Concept 1of the present invention, apparatus including a testing device fortesting for the presence of particulate in a liquid, the testing deviceincluding:

a liquid container for containing the liquid;

a filter, disposed in or downstream of the liquid container;

a liquid-pressure source, which is arranged to apply pressure to drivethe liquid contained in the liquid container through the filter; and

a filter chamber that is (a) disposed downstream of the liquidcontainer, (b) shaped so as to define an inlet, and (c) in fluidcommunication with the filter.

Inventive Concept 2. The apparatus according to Inventive Concept 1,wherein the inlet of the filter chamber has an inlet area that equalsbetween 4% and 40% of a filter area of the filter.Inventive Concept 3. The apparatus according to Inventive Concept 1,wherein the inlet of the filter chamber has an inlet area that is lessthan a greatest cross-sectional area of the filter chamber, the inletarea and the greatest cross-sectional area measured in respective planesparallel to each other.Inventive Concept 4. The apparatus according to Inventive Concept 1,wherein the filter chamber has an internal volume of between 0.5 and 12ml.Inventive Concept 5. The apparatus according to Inventive Concept 4,wherein the internal volume is between 0.5 and 4 ml.Inventive Concept 6. The apparatus according to Inventive Concept 4,wherein the internal volume is between 1 and 5 ml.Inventive Concept 7. The apparatus according to Inventive Concept 1,wherein the filter chamber has an internal surface area that equalsbetween 10% and 150% of a filter surface area of an upstream side of thefilter.Inventive Concept 8. The apparatus according to Inventive Concept 1,wherein the filter chamber has an internal length of between 0.5 and 10cm.Inventive Concept 9. The apparatus according to Inventive Concept 1,wherein the filter chamber has an internal length equal to between 50%and 2000% of a greatest internal width of the filter chamber.Inventive Concept 10. The apparatus according to Inventive Concept 1,wherein the filter chamber is nipple-shaped.Inventive Concept 11. The apparatus according to Inventive Concept 1,wherein the filter chamber includes one or more pressure-activatedvalves, not disposed at the inlet of the filter chamber.Inventive Concept 12. The apparatus according to Inventive Concept 1,wherein the liquid-pressure source includes a vacuum pump disposeddownstream of filter.Inventive Concept 13. The apparatus according to Inventive Concept 1,wherein the liquid-pressure source includes a positive-pressure pumpdisposed upstream of the filter.Inventive Concept 14. The apparatus according to Inventive Concept 1,wherein the filter has a filter surface area of an upstream side of thefilter that equals between 0.3 and 100 cm2.Inventive Concept 15. The apparatus according to Inventive Concept 14,wherein the filter surface area equals between 0.3 and 30 cm2.Inventive Concept 16. The apparatus according to Inventive Concept 1,wherein the filter is configured to trap at least 40% of group Astreptococcus bacteria and allow passage of the liquid.Inventive Concept 17. The apparatus according to Inventive Concept 1,wherein the filter is configured to trap at least 40% of the particulateto be tested and allow passage of the liquid.Inventive Concept 18. The apparatus according to any one of InventiveConcepts 1-17, wherein the testing device further includes a wasteliquid receptacle, which is coupled to the liquid container downstreamof the filter, and wherein the liquid-pressure source is arranged toapply pressure to drive the liquid contained in the liquid containerthrough the filter and then into the waste liquid receptacle.Inventive Concept 19. The apparatus according to Inventive Concept 18,wherein the liquid-pressure source includes a plunger, which includes aplunger head that is shaped so as to be insertable into the liquidcontainer, and wherein the plunger is shaped so as to define the wasteliquid receptacle.Inventive Concept 20. The apparatus according to Inventive Concept 18,wherein the waste liquid receptacle contains an antibacterial agent.Inventive Concept 21. The apparatus according to Inventive Concept 18,wherein the filter chamber is laterally surrounded by at least a portionof the waste liquid receptacle.Inventive Concept 22. The apparatus according to Inventive Concept 18,wherein the filter chamber is disposed within the waste liquidreceptacle.Inventive Concept 23. The apparatus according to any one of InventiveConcepts 1-17, wherein the filter is removably disposed upstream of thefilter chamber with the filter partially covering the inlet of thefilter chamber.Inventive Concept 24. The apparatus according to Inventive Concept 23,wherein the inlet of the filter chamber has an inlet centroid that isdisposed within a distance of a filter centroid, the distance equal to50% of a greatest dimension of the filter, when the filter is removablydisposed upstream of the filter chamber with the filter partiallycovering the inlet of the filter chamber.Inventive Concept 25. The apparatus according to Inventive Concept 23,wherein the testing device further includes a support for the filter,disposed at least partially between the inlet of the filter chamber andthe filter.Inventive Concept 26. The apparatus according to Inventive Concept 23,wherein the apparatus further includes an elongate member configured topush at least a portion of the filter into the filter chamber.Inventive Concept 27. The apparatus according to Inventive Concept 23,wherein the liquid-pressure source includes a plunger, which includes aplunger head that is shaped so as to be insertable into the liquidcontainer, and wherein the plunger head is configured to push at least aportion of the filter into the filter chamber.Inventive Concept 28. The apparatus according to Inventive Concept 23,wherein the testing device further includes a frangible seal thatremovably blocks liquid flow into the inlet of the filter chamber.Inventive Concept 29. The apparatus according to Inventive Concept 23,wherein the filter chamber includes one or more valves, not disposed atthe inlet of the filter chamber.Inventive Concept 30. The apparatus according to Inventive Concept 29,wherein the one or more valves include one or more pressure-activatedvalves.Inventive Concept 31. The apparatus according to Inventive Concept 30,wherein the one or more valves include one or morenon-pressure-activated valves.32. The apparatus according to Inventive Concept 29,

wherein the liquid container is shaped so as to define one or moreopenings through a wall of the liquid container,

wherein the one or more openings are downstream of the filter when thefilter is removably disposed upstream of the filter chamber with thefilter partially covering the inlet of the filter chamber, and

wherein the filter chamber is not disposed so as to receive the liquidthat is driven through the one or more openings.

Inventive Concept 33. The apparatus according to any one of InventiveConcepts 1-17, wherein the filter is disposed at least partially withinthe filter chamber.Inventive Concept 34. The apparatus according to Inventive Concept 33,wherein the filter is disposed entirely within the filter chamber.Inventive Concept 35. The apparatus according to Inventive Concept 33,wherein the filter is shaped as a receptacle.Inventive Concept 36. The apparatus according to any one of InventiveConcepts 1-17, wherein the liquid-pressure source includes a plunger,which includes a plunger head that is shaped so as to be insertable intothe liquid container.Inventive Concept 37. The apparatus according to Inventive Concept 36,wherein the plunger is shaped so as to define the filter chamber.Inventive Concept 38. The apparatus according to any one of InventiveConcepts 1-17, wherein the testing device further includes one or moreheating elements which are configured to heat the filter at a generallyconstant temperature, the temperature in the range of 20 and 50 degreesC.Inventive Concept 39. The apparatus according to Inventive Concept 38,wherein the temperature is in the range of 30 to 40 degrees C.Inventive Concept 40. The apparatus according to Inventive Concept 38,wherein the liquid container includes, upstream of the filter, afrangible dividing waterproof or water-resistant membrane that isolatesthe filter from the liquid in the liquid container.Inventive Concept 41. The apparatus according to Inventive Concept 38,wherein the liquid-pressure source includes a plunger, which includes aplunger head that is shaped so as to be insertable into the liquidcontainer, and wherein the one or more heating elements are disposed inthe plunger.Inventive Concept 42. The apparatus according to any one of InventiveConcepts 1-17, wherein the liquid container is shaped so as to defineupstream and downstream openings, and wherein an area of the upstreamopening is greater than the area of the downstream opening.Inventive Concept 43. The apparatus according to Inventive Concept 42,wherein the liquid container includes an upstream end portion thatincludes the upstream opening, and wherein the upstream end portion isconical.Inventive Concept 44. The apparatus according to Inventive Concept 43,wherein a diameter of the upstream opening is at least 20% greater thana diameter of the downstream opening.Inventive Concept 45. The apparatus according to any one of InventiveConcepts 1-17, wherein the apparatus further includes sterile packaging,in which at least the liquid container, the filter chamber, and thefilter are removably disposed.Inventive Concept 46. The apparatus according to any one of InventiveConcepts 1-17, wherein the apparatus further includes at least onecontainer including an extraction reagent.Inventive Concept 47. The apparatus according to Inventive Concept 46,wherein the apparatus further includes a test strip.

There is further provided, in accordance with an Inventive Concept 48 ofthe present invention, a method including:

applying pressure to drive liquid contained in a liquid container of atesting device through a filter of the testing device, wherein thefilter is disposed in or downstream of the liquid container, and whereinthe liquid includes at least one substance selected from the group ofsubstances consisting of gargled fluid, saliva not swabbed from a throatof a patient, and an incubated culture medium containing a biologicalsample; and

thereafter, testing, within a filter chamber of the testing device, forthe presence of particulate trapped by the filter while the filter isdisposed at least partially in the filter chamber, wherein the filterchamber is (a) disposed downstream of the liquid container, (b) shapedso as to define an inlet, and (c) in fluid communication with thefilter.

Inventive Concept 49. The method according to Inventive Concept 48,wherein testing includes applying an extraction reagent to the filterwhile the filter is in the filter chamber.Inventive Concept 50. The method according to Inventive Concept 49,wherein testing further includes after applying the extraction reagent,inserting a test strip into the filter chamber and examining the teststrip to test for the presence of the particulate.Inventive Concept 51. The method according to Inventive Concept 48,further including taking a sample from the filter, and testing thesample, outside the testing device, for the presence of the particulate.Inventive Concept 52. The method according to Inventive Concept 51,wherein testing the sample outside the testing device includes testingthe sample outside the testing device without first incubating thesample.Inventive Concept 53. The method according to Inventive Concept 52,wherein testing the sample outside the testing device includesperforming a technique selected from the group consisting of: a nucleicacid amplification rapid strep test (RST) technique and real-timequantitative polymerase chain reaction (qPCR) assaying.Inventive Concept 54. The method according to Inventive Concept 51,wherein testing the sample outside the testing device includesincubating the sample outside the testing device and subsequentlytesting the sample outside the testing device.Inventive Concept 55. The method according to Inventive Concept 54,wherein testing the sample outside the testing device includesperforming a technique selected from the group consisting of: lateralflow immunoassaying, an ELISA-based rapid strep test (RST), anantibody-coated-beads-based RST, a nucleic-acid-based RST, and afluorescent immunoassaying (FIA).Inventive Concept 56. The method according to Inventive Concept 48,wherein the liquid includes the gargled fluid.Inventive Concept 57. The method according to Inventive Concept 48,wherein the liquid includes the saliva not swabbed from the throat ofthe patient.Inventive Concept 58. The method according to Inventive Concept 57,wherein the saliva not swabbed from the throat of the patient is salivaspit by the patient.Inventive Concept 59. The method according to Inventive Concept 48,wherein the liquid includes the incubated culture medium containing thebiological sample.Inventive Concept 60. The method according to Inventive Concept 48,wherein applying the pressure includes pushing a plunger including aplunger head inserted into the liquid container.Inventive Concept 61. The method according to Inventive Concept 60,wherein the plunger is shaped so as to define the filter chamber.Inventive Concept 62. The method according to Inventive Concept 48,wherein applying the pressure includes applying positive pressure usinga positive-pressure pump disposed upstream of the filter.Inventive Concept 63. The method according to Inventive Concept 48,wherein applying the pressure includes applying negative pressure usinga vacuum pump disposed downstream of the filter.Inventive Concept 64. The method according to Inventive Concept 48,wherein applying the pressure includes applying the pressure while thefilter is removably disposed upstream of the filter chamber with thefilter partially covering the inlet of the filter chamber, and whereintesting includes pushing at least a portion of the filter into thefilter chamber.Inventive Concept 65. The method according to Inventive Concept 64,wherein pushing includes pushing the at least a portion of the filterinto the filter chamber using an elongate member.Inventive Concept 66. The method according to Inventive Concept 65,wherein pushing the at least a portion of the filter into the filterchamber includes taking a sample from the filter using the elongatemember, and testing the sample, outside the testing device, for thepresence of the particulate.Inventive Concept 67. The method according to Inventive Concept 64,wherein the testing device further includes a frangible seal thatremovably blocks liquid flow into the inlet of the filter chamber, andwherein the method further includes, after applying the pressure andbefore testing for the presence of the particulate trapped by thefilter, breaking the frangible seal.Inventive Concept 68. The method according to Inventive Concept 64,wherein the filter chamber includes one or more valves, not disposed atthe inlet of the filter chamber.Inventive Concept 69. The method according to Inventive Concept 68,wherein the one or more valves include one or more pressure-activatedvalves.Inventive Concept 70. The method according to Inventive Concept 69,wherein the one or more valves include one or morenon-pressure-activated valves.Inventive Concept 71. The method according to Inventive Concept 48,wherein applying the pressure includes applying the pressure while thefilter is disposed at least partially within the filter chamber.Inventive Concept 72. The method according to Inventive Concept 71,wherein applying the pressure includes applying the pressure while thefilter is disposed entirely within the filter chamber.Inventive Concept 73. The method according to Inventive Concept 71,wherein the filter is shaped as a receptacle.Inventive Concept 74. The method according to Inventive Concept 48,further including, before applying the pressure, taking a sample of theliquid, and testing the sample, outside the testing device, for thepresence of the particulate.

There is still further provided, in accordance with an Inventive Concept75 of the present invention, a method including:

applying pressure to drive liquid contained in a liquid container of atesting device (a) through a filter of the testing device and (b) thenthrough one or more valves of the testing device, wherein the filter isdisposed in or downstream of the liquid container, wherein the one ormore valves are disposed downstream of the filter, and wherein theliquid includes at least one substance selected from the group ofsubstances consisting of gargled fluid, saliva not swabbed from a throatof a patient, and an incubated culture medium containing a biologicalsample; and

thereafter, testing, within the testing device, for the presence ofparticulate trapped by the filter while the one or more valves areclosed and the filter is disposed in the testing device.

Inventive Concept 76. The method according to Inventive Concept 75,wherein testing includes applying an extraction reagent to the filter.Inventive Concept 77. The method according to Inventive Concept 76,wherein testing further includes after applying the extraction reagent,inserting a test strip into the testing device and examining the teststrip to test for the presence of the particulate.Inventive Concept 78. The method according to Inventive Concept 75,wherein the liquid includes the gargled fluid.Inventive Concept 79. The method according to Inventive Concept 75,wherein the liquid includes the saliva not swabbed from the throat ofthe patient.Inventive Concept 80. The method according to Inventive Concept 79,wherein the saliva not swabbed from the throat of the patient is salivaspit by the patient.Inventive Concept 81. The method according to Inventive Concept 75,wherein the liquid includes the incubated culture medium containing thebiological sample.Inventive Concept 82. The method according to Inventive Concept 75,wherein the liquid container has an internal volume of between 0.5 and500 ml.Inventive Concept 83. The method according to Inventive Concept 75,wherein applying the pressure includes pushing a plunger including aplunger head inserted into the liquid container.Inventive Concept 84. The method according to Inventive Concept 75,wherein applying the pressure includes applying positive pressure usinga positive-pressure pump disposed upstream of the filter.Inventive Concept 85. The method according to Inventive Concept 75,wherein applying the pressure includes applying negative pressure usinga vacuum pump disposed downstream of the one or more valves.Inventive Concept 86. The method according to Inventive Concept 75,wherein the one or more valves include one or more pressure-activatedvalves.Inventive Concept 87. The method according to Inventive Concept 75,wherein the one or more valves include one or morenon-pressure-activated valves.Inventive Concept 88. The method according to Inventive Concept 87,wherein the testing device is configured to automatically close the oneor more non-pressure-activated valves after the pressure is applied todrive the liquid through the filter and then through the one or morenon-pressure-activated valves.Inventive Concept 89. The method according to Inventive Concept 87,wherein the one or more non-pressure-activated valves include two discsthat are shaped so as to define respective sets of openings, and whereinthe one or more non-pressure-activated valves are configured to assumeopen and closed states when the two sets of openings are aligned andnon-aligned with each other.Inventive Concept 90. The method according to Inventive Concept 87,wherein applying the pressure includes pushing a plunger including aplunger head inserted into the liquid container, and wherein the testingdevice is configured to automatically close the one or morenon-pressure-activated valves after the plunger applies the pressure todrive the liquid contained in the liquid container through the filterand then through the one or more non-pressure-activated valves.Inventive Concept 91. The method according to Inventive Concept 90,wherein the testing device is configured such that motion of the plungerautomatically closes the one or more non-pressure-activated valves afterthe plunger applies the pressure to drive the liquid contained in theliquid container through the filter and then through the one or morenon-pressure-activated valves.Inventive Concept 92. The method according to Inventive Concept 91,wherein pushing the plunger include rotating the plunger, and whereinthe testing device is configured such that rotational motion of theplunger automatically closes the one or more non-pressure-activatedvalves after the plunger applies the pressure to drive the liquidcontained in the liquid container through the filter and then throughthe one or more non-pressure-activated valves.Inventive Concept 93. The method according to Inventive Concept 92,wherein the plunger is shaped so as to define one or more plungerthreads, and wherein an internal wall of the liquid container is shapedso as to define one or more liquid-container threads that engage the oneor more plunger threads such that rotation of the plunger advances theplunger in a downstream direction within the liquid container.Inventive Concept 94. The method according to Inventive Concept 92,

wherein the one or more non-pressure-activated valves include two discsthat are shaped so as to define respective sets of openings, and whereinthe one or more non-pressure-activated valves are configured to assumeopen and closed states when the two sets of openings are aligned andnon-aligned with each other,

wherein pushing the plunger include rotating the plunger, and

wherein the testing device is configured such that rotational motion ofthe plunger automatically closes the one or more non-pressure-activatedvalves by rotating at least one of the two discs with respect to theother of the discs, after the plunger applies the pressure to drive theliquid contained in the liquid container through the filter and thenthrough the one or more non-pressure-activated valves.

Inventive Concept 95. The method according to Inventive Concept 75,wherein applying the pressure includes applying the pressure to drivethe liquid contained in the liquid container through the filter, thenthrough the one or more valves, and then into a waste liquid receptacleof the testing device, wherein the waste liquid receptacle is coupled tothe liquid container downstream of the one or more valves.Inventive Concept 96. The method according to Inventive Concept 95,

wherein applying the pressure includes pushing a plunger including aplunger head inserted into the liquid container, and

wherein the plunger is shaped so as to define the waste liquidreceptacle.

Inventive Concept 97. The method according to Inventive Concept 95,wherein the waste liquid receptacle contains an antibacterial agent.Inventive Concept 98. The method according to Inventive Concept 75,wherein the testing device further includes a filter chamber that is (a)disposed downstream of the liquid container, (b) shaped so as to definean inlet, and (c) in fluid communication with filter.Inventive Concept 99. The method according to Inventive Concept 98,

wherein applying the pressure includes pushing a plunger including aplunger head inserted into the liquid container, and

wherein the plunger is shaped so as to define the filter chamber.

Inventive Concept 100. The method according to Inventive Concept 98,

wherein the liquid-pressure source is arranged to apply pressure todrive the liquid contained in the liquid container through the filter,then through the one or more valves, and then into a waste liquidreceptacle of the testing device, wherein the waste liquid receptacle iscoupled to the liquid container downstream of the one or more valves,and

wherein the filter chamber is laterally surrounded by at least a portionof the waste liquid receptacle.

Inventive Concept 101. The method according to Inventive Concept 98,

wherein the liquid-pressure source is arranged to apply pressure todrive the liquid contained in the liquid container through the filter,then through the one or more valves, and then into a waste liquidreceptacle of the testing device, wherein the waste liquid receptacle iscoupled to the liquid container downstream of the one or more valves,and

wherein the filter chamber is disposed within the waste liquidreceptacle.

Inventive Concept 102. The method according to Inventive Concept 98,wherein the inlet of the filter chamber has an inlet area that is lessthan a greatest cross-sectional area of the filter chamber, the inletarea and the greatest cross-sectional area measured in respective planesparallel to each other.Inventive Concept 103. The method according to Inventive Concept 98,wherein the filter chamber is nipple-shaped.Inventive Concept 104. The method according to Inventive Concept 98,wherein the filter chamber includes at least one of the one or morevalves, not disposed at the inlet of the filter chamber.Inventive Concept 105. The method according to Inventive Concept 98,wherein applying the pressure includes applying the pressure while thefilter is removably disposed upstream of the filter chamber with thefilter partially covering the inlet of the filter chamber.Inventive Concept 106. The method according to Inventive Concept 105,wherein the method further includes, after applying the pressure andbefore testing for the presence of the particulate trapped by thefilter, pushing at least a portion of the filter into the filterchamber.Inventive Concept 107. The method according to Inventive Concept 106,wherein applying the pressure includes pushing a plunger including aplunger head inserted into the liquid container, and wherein pushing theat least a portion of the filter into the filter chamber includespushing the at least a portion of the filter into the filter chamberusing the plunger head.Inventive Concept 108. The method according to Inventive Concept 106,wherein pushing includes pushing the at least a portion of the filterinto the filter chamber using an elongate member.Inventive Concept 109. The method according to Inventive Concept 108,wherein pushing the at least a portion of the filter into the filterchamber includes taking a sample from the filter using the elongatemember, and testing the sample, outside the testing device, for thepresence of the particulate.Inventive Concept 110. The method according to Inventive Concept 105,wherein the inlet of the filter chamber has an inlet centroid that isdisposed less than a distance from a filter centroid, the distance equalto 50% of a greatest dimension of the filter.Inventive Concept 111. The method according to Inventive Concept 105,

wherein the testing device further includes a frangible seal thatremovably blocks liquid flow into the inlet of the filter chamber, and

wherein the method further includes, after applying the pressure andbefore testing for the presence of the particulate trapped by thefilter, breaking the frangible seal.

Inventive Concept 112. The method according to Inventive Concept 98,wherein the filter chamber is not disposed so as to receive the liquidthat is driven through at least one of the one or more valves.Inventive Concept 113. The method according to Inventive Concept 98,wherein the filter chamber includes at least one of the one or morevalves, not disposed at the inlet of the filter chamber.Inventive Concept 114. The method according to Inventive Concept 113,

wherein the liquid container is shaped so as to define one or moreopenings through a wall of the liquid container,

wherein the one or more openings are downstream of the filter when thefilter is removably disposed upstream of the filter chamber with thefilter partially covering the inlet of the filter chamber,

wherein the filter chamber is not disposed so as to receive the liquidthat is driven through the one or more openings, and

wherein applying the pressure includes applying the pressure to drivethe liquid (i) partially through (a) the filter and (b) one or more ofthe one or more valves of the testing device and (ii) partially throughthe one or more openings.

Inventive Concept 115. The method according to Inventive Concept 98,wherein the filter is disposed at least partially within the filterchamber.Inventive Concept 116. The method according to Inventive Concept 115,wherein the filter is disposed entirely within the filter chamber.Inventive Concept 117. The method according to Inventive Concept 115,wherein the filter is shaped as a receptacle.Inventive Concept 118. The method according to Inventive Concept 75,wherein the filter is configured to trap at least 40% of group Astreptococcus bacteria and allow passage of the liquid.Inventive Concept 119. The method according to Inventive Concept 75,wherein the filter is configured to trap at least 40% of theparticulate.Inventive Concept 120. The method according to Inventive Concept 75,wherein the method further includes, before testing for the presence ofthe particulate trapped by the filter, activating one or more heatingelements which are configured to heat the filter at a generally constanttemperature, the temperature in the range of 20 and 50 degrees C.Inventive Concept 121. The method according to Inventive Concept 120,wherein the temperature is in the range of 30 to 40 degrees C.Inventive Concept 122. The method according to Inventive Concept 120,wherein the one or more heating elements are disposed within the testingdevice.Inventive Concept 123. The method according to Inventive Concept 122,wherein applying the pressure includes pushing a plunger including aplunger head inserted into the liquid container, and wherein the one ormore heating elements are disposed in the plunger.Inventive Concept 124. The method according to Inventive Concept 75,wherein the method further includes, before most of the liquid initiallycontained in the testing device has been driven through the filter,activating one or more heating elements which are configured to heat thefilter at a generally constant temperature, the temperature in the rangeof 20 and 50 degrees C.Inventive Concept 125. The method according to Inventive Concept 124,wherein the temperature is in the range of 30 to 40 degrees C.Inventive Concept 126. The method according to Inventive Concept 124,wherein activating the one or more heating elements includes activatingthe one or more heating elements before any of the liquid initiallycontained in the testing device has been driven through the filter.Inventive Concept 127. The method according to Inventive Concept 126,

wherein the liquid container includes, upstream of the filter, afrangible dividing waterproof or water-resistant membrane that isolatesthe filter from the liquid in the liquid container, and

wherein the method further includes breaking the frangible dividingwaterproof or water-resistant membrane before driving the liquid throughthe filter.

Inventive Concept 128. The method according to Inventive Concept 126,wherein activating the one or more heating elements includes orientingthe testing device with the filter above the liquid, such that theliquid is not in contact with the filter during heating.Inventive Concept 129. The method according to Inventive Concept 124,wherein the one or more heating elements are disposed within the testingdevice.Inventive Concept 130. The method according to Inventive Concept 75,

wherein the one or more valves are one or more first valves, and

wherein the testing device further includes one or more second pressurerelief valves, which are in fluid communication with the liquidcontainer and are disposed upstream of the filter.

Inventive Concept 131. The method according to Inventive Concept 130,

wherein the liquid-pressure source is arranged to apply pressure todrive the liquid contained in the liquid container through the filter,then through the one or more valves, and then into a waste liquidreceptacle of the testing device, wherein the waste liquid receptacle iscoupled to the liquid container downstream of the one or more valves,and

wherein the one or more second pressure relief valves are in fluidcommunication with the waste liquid receptacle not via the filter.

Inventive Concept 132. The method according to Inventive Concept 130,

wherein the liquid-pressure source includes a plunger, which includes(a) a plunger shaft and (b) a plunger head that is disposed at adownstream end portion of the plunger shaft and shaped so as to beinsertable into the liquid container,

wherein the testing device includes one or more unfiltered liquidreceptacles,

wherein the one or more second pressure relief valves are in fluidcommunication with the one or more unfiltered liquid receptacles, and

wherein the method further includes, after applying the pressure, takinga sample of the liquid in the one or more unfiltered liquid receptacles,and testing the sample, outside the testing device, for the presence ofthe particulate.

Inventive Concept 133. The method according to Inventive Concept 132,wherein the one or more unfiltered liquid receptacles are disposed alongthe plunger shaft.Inventive Concept 134. The method according to Inventive Concept 133,wherein the one or more unfiltered liquid receptacles are removablycoupled to the plunger.Inventive Concept 135. The method according to Inventive Concept 130,

wherein the one or more first valves include one or more firstpressure-activated valves configured to open upon exposure to a firstpressure gradient across the one or more first pressure-activatedvalves, and

wherein the one or more second pressure relief valves are configured toopen upon exposure to a second pressure gradient across the one or moresecond pressure relief valves, the second pressure gradient greater thanthe first pressure gradient.

Inventive Concept 136. The method according to Inventive Concept 75,wherein the method further includes, before applying the pressure,removing the liquid container, the one or more valves, and the filterfrom sterile packaging.Inventive Concept 137. The method according to Inventive Concept 75,wherein the particulate includes biological particulate.Inventive Concept 138. The method according to Inventive Concept 137,wherein the biological particulate is selected from the group consistingof: a microorganism, a fungus, a bacterium, a spore, a virus, a mite, abiological cell, a biological antigen, a protein, a protein antigen, anda carbohydrate antigen.Inventive Concept 139. The method according to Inventive Concept 75,wherein testing for the presence of the particulate includes applying anextraction reagent to the filter after applying the pressure.Inventive Concept 140. The method according to Inventive Concept 139,wherein testing for the presence of the particulate includes using atest strip.Inventive Concept 141. The method according to Inventive Concept 75,further including, after applying the pressure, taking a sample from thefilter, and testing the sample, outside the testing device, for thepresence of the particulate trapped by the filter.Inventive Concept 142. The method according to Inventive Concept 75,further including, before applying the pressure, taking a sample of theliquid, and testing the sample, outside the testing device, for thepresence of the particulate.Inventive Concept 143. The method according to Inventive Concept 75,further including taking a sample from the filter, and testing thesample, outside the testing device, for the presence of the particulate.Inventive Concept 144. The method according to Inventive Concept 143,wherein testing the sample outside the testing device includes testingthe sample outside the testing device without first incubating thesample.Inventive Concept 145. The method according to Inventive Concept 144,wherein testing the sample outside the testing device includesperforming a technique selected from the group consisting of: a nucleicacid amplification rapid strep test (RST) technique and real-timequantitative polymerase chain reaction (qPCR) assaying.Inventive Concept 146. The method according to Inventive Concept 143,wherein testing the sample outside the testing device includesincubating the sample outside the testing device and subsequentlytesting the sample outside the testing device.Inventive Concept 147. The method according to Inventive Concept 146,wherein testing the sample outside the testing device includesperforming a technique selected from the group consisting of: lateralflow immunoassaying, an ELISA-based rapid strep test (RST), anantibody-coated-beads-based RST, a nucleic-acid-based RST, and afluorescent immunoassaying (FIA).

There is additionally provided, in accordance with an Inventive Concept148 of the present invention, apparatus including a testing device fortesting for the presence of particulate in a liquid, the testing deviceincluding:

a liquid container for containing the liquid, the liquid containershaped so as to define upstream and downstream openings;

a filter, removably disposed in the liquid container; and

a plunger head that (a) is shaped so as to be insertable into the liquidcontainer so as to form a movable seal with a wall of the liquidcontainer, and (b) is arranged such that when pushed, the plunger headapplies pressure to drive the liquid contained in the liquid containerthrough the filter and then through the downstream opening,

wherein the testing device is configured such that rotation of theplunger head radially compresses the filter toward a centrallongitudinal axis of the plunger head.

Inventive Concept 149. The apparatus according to Inventive Concept 148,wherein the testing device is configured such that the rotation of theplunger head crushes the filter.Inventive Concept 150. The apparatus according to Inventive Concept 149,wherein the plunger head includes a protrusion, and wherein the testingdevice is configured such that the rotation of the plunger head causesthe protrusion to move radially toward the central longitudinal axis ofthe plunger head.Inventive Concept 151. The apparatus according to Inventive Concept 150,

wherein the liquid container is shaped so as to define a filter-supportsurface surrounding the downstream opening,

wherein the filter-support surface supports a radial portion of thefilter excluding a central portion of the filter,

wherein the filter-support surface is shaped so as to define a spiralgroove,

wherein the protrusion is configured to engage the spiral groove throughthe filter, and

wherein the testing device is configured such that the rotation of theplunger head causes the spiral groove to guide the protrusion radiallytoward the central longitudinal axis of the plunger head.

There is yet additionally provided, in accordance with an InventiveConcept 152 of the present invention, a method including:

inserting a plunger head into a liquid container of a testing device soas to form a movable seal with a wall of the liquid container;

pushing the plunger head to apply pressure to drive liquid contained inthe liquid container through a filter of the testing device and thenthrough a downstream opening of the liquid container, which also has anupstream opening, wherein the filter is removably disposed in the liquidcontainer; and

rotating the plunger head to radially crush the filter toward a centrallongitudinal axis of the plunger head.

Inventive Concept 153. The method according to Inventive Concept 152,further including, after rotating the plunger head, testing the filterfor the presence of particulate trapped by the filter.Inventive Concept 154. The method according to Inventive Concept 152,wherein rotating the plunger head crushes the filter.Inventive Concept 155. The method according to Inventive Concept 154,wherein the plunger head includes a protrusion, and wherein rotating theplunger head causes the protrusion to move radially toward the centrallongitudinal axis of the plunger head.Inventive Concept 156. The method according to Inventive Concept 155,

wherein the liquid container is shaped so as to define a filter-supportsurface surrounding the downstream opening,

wherein the filter-support surface supports a radial portion of thefilter excluding a central portion of the filter,

wherein the filter-support surface is shaped so as to define a spiralgroove,

wherein the protrusion is configured to engage the spiral groove throughthe filter, and

wherein rotating the plunger head causes the spiral groove to guide theprotrusion radially toward the central longitudinal axis of the plungerhead.

Inventive Concept There is further provided, in accordance with anInventive Concept 157 of the present invention, apparatus including atesting device for testing for the presence of particulate in a liquid,the testing device including:

a liquid container for containing the liquid, wherein the liquidcontainer has an internal volume of between 0.5 and 500 ml;

one or more valves;

a filter, disposed in or downstream of the liquid container and upstreamof the one or more valves; and

a plunger, which (a) includes a plunger head that is shaped so as to beinsertable into the liquid container, and (b) is arranged to applypressure to drive the liquid contained in the liquid container throughthe filter and then through the one or more valves.

Inventive Concept 158. The apparatus according to Inventive Concept 157,wherein the one or more valves include one or more pressure-activatedvalves.Inventive Concept 159. The apparatus according to Inventive Concept 157,wherein the one or more valves include one or morenon-pressure-activated valves.Inventive Concept 160. The apparatus according to Inventive Concept 159,wherein the one or more non-pressure-activated valves include two discsthat are shaped so as to define respective sets of openings, and whereinthe one or more non-pressure-activated valves are configured to assumeopen and closed states when the two sets of openings are aligned andnon-aligned with each other.Inventive Concept 161. The apparatus according to Inventive Concept 159,wherein the testing device is configured to automatically close the oneor more non-pressure-activated valves after the plunger applies thepressure to drive the liquid contained in the liquid container throughthe filter and then through the one or more non-pressure-activatedvalves.Inventive Concept 162. The apparatus according to Inventive Concept 161,wherein the testing device is configured such that motion of the plungerautomatically closes the one or more non-pressure-activated valves afterthe plunger applies the pressure to drive the liquid contained in theliquid container through the filter and then through the one or morenon-pressure-activated valves.Inventive Concept 163. The apparatus according to Inventive Concept 162,wherein the testing device is configured such that rotational motion ofthe plunger automatically closes the one or more non-pressure-activatedvalves after the plunger applies the pressure to drive the liquidcontained in the liquid container through the filter and then throughthe one or more non-pressure-activated valves.Inventive Concept 164. The apparatus according to Inventive Concept 163,wherein the plunger is shaped so as to define one or more plungerthreads, and wherein an internal wall of the liquid container is shapedso as to define one or more liquid-container threads that engage the oneor more plunger threads such that rotation of the plunger advances theplunger in a downstream direction within the liquid container.Inventive Concept 165. The apparatus according to Inventive Concept 163,

wherein the one or more non-pressure-activated valves include two discsthat are shaped so as to define respective sets of openings, and whereinthe one or more non-pressure-activated valves are configured to assumeopen and closed states when the two sets of openings are aligned andnon-aligned with each other, and

wherein the testing device is configured such that rotational motion ofthe plunger automatically closes the one or more non-pressure-activatedvalves by rotating at least one of the two discs with respect to theother of the discs, after the plunger applies the pressure to drive theliquid contained in the liquid container through the filter and thenthrough the one or more non-pressure-activated valves.

Inventive Concept 166. The apparatus according to Inventive Concept 157,wherein the filter has a filter surface area of an upstream side of thefilter that equals between 0.3 and 100 cm2.Inventive Concept 167. The apparatus according to Inventive Concept 166,wherein the filter surface area equals between 0.3 and 30 cm2.Inventive Concept 168. The apparatus according to Inventive Concept 157,wherein the filter is configured to trap at least 40% of group Astreptococcus bacteria and allow passage of the liquid.Inventive Concept 169. The apparatus according to Inventive Concept 157,wherein the filter is configured to trap at least 40% of the particulateto be tested and allow passage of the liquid.Inventive Concept 170. The apparatus according to any one of InventiveConcepts 157-169, wherein the testing device further includes a wasteliquid receptacle, which is coupled to the liquid container downstreamof the one or more valves, and wherein the plunger is arranged to applypressure to drive the liquid contained in the liquid container throughthe filter, then through the one or more valves, and then into the wasteliquid receptacle.Inventive Concept 171. The apparatus according to Inventive Concept 170,wherein the plunger is shaped so as to define the waste liquidreceptacle.Inventive Concept 172. The apparatus according to Inventive Concept 170,wherein the waste liquid receptacle contains an antibacterial agent.Inventive Concept 173. The apparatus according to any one of InventiveConcepts 157-169, wherein the testing device further includes a filterchamber that is (a) disposed downstream of the liquid container, (b)shaped so as to define an inlet, and (c) in fluid communication with thefilter.Inventive Concept 174. The apparatus according to Inventive Concept 173,wherein the plunger is shaped so as to define the filter chamber.Inventive Concept 175. The apparatus according to Inventive Concept 173,

wherein the testing device further includes a waste liquid receptacle,which is coupled to the liquid container downstream of the filter,

wherein the plunger is arranged to apply pressure to drive the liquidcontained in the liquid container through the filter and then into thewaste liquid receptacle, and

wherein the filter chamber is laterally surrounded by at least a portionof the waste liquid receptacle.

Inventive Concept 176. The apparatus according to Inventive Concept 173,

wherein the testing device further includes a waste liquid receptacle,which is coupled to the liquid container downstream of the filter,

wherein the plunger is arranged to apply pressure to drive the liquidcontained in the liquid container through the filter and then into thewaste liquid receptacle, and

wherein the filter chamber is disposed within the waste liquidreceptacle.

Inventive Concept 177. The apparatus according to Inventive Concept 173,wherein the inlet of the filter chamber has an inlet area that equalsbetween 4% and 40% of a filter surface area of an upstream side of thefilter.Inventive Concept 178. The apparatus according to Inventive Concept 173,wherein the inlet of the filter chamber has an inlet area that is lessthan a greatest cross-sectional area of the filter chamber, the inletarea and the greatest cross-sectional area measured in respective planesparallel to each other.Inventive Concept 179. The apparatus according to Inventive Concept 173,wherein the filter chamber has an internal volume of between 0.5 and 12ml.Inventive Concept 180. The apparatus according to Inventive Concept 179,wherein the internal volume is between 0.5 and 4 ml.Inventive Concept 181. The apparatus according to Inventive Concept 179,wherein the internal volume is between 1 and 5 ml.Inventive Concept 182. The apparatus according to Inventive Concept 173,wherein the filter chamber has an internal surface area that equalsbetween 10% and 150% of a filter surface area of an upstream side of thefilter.Inventive Concept 183. The apparatus according to Inventive Concept 173,wherein the filter chamber has an internal length of between 0.5 and 10cm.Inventive Concept 184. The apparatus according to Inventive Concept 173,wherein the filter chamber has an internal length equal to between 50%and 2000% of a greatest internal width of the filter chamber.Inventive Concept 185. The apparatus according to Inventive Concept 173,wherein the filter chamber is nipple-shaped.Inventive Concept 186. The apparatus according to Inventive Concept 173,wherein the filter chamber includes at least one of the one or morevalves, not disposed at the inlet of the filter chamber.Inventive Concept 187. The apparatus according to Inventive Concept 173,wherein the filter is removably disposed upstream of the filter chamberwith the filter partially covering the inlet of the filter chamber.Inventive Concept 188. The apparatus according to Inventive Concept 187,wherein the inlet of the filter chamber has an inlet centroid that isdisposed less than a distance from a filter centroid, the distance equalto 50% of a greatest dimension of the filter, when the filter isremovably disposed upstream of the filter chamber with the filterpartially covering the inlet of the filter chamber.Inventive Concept 189. The apparatus according to Inventive Concept 187,wherein the testing device further includes a support for the filter,disposed at least partially between the inlet of the filter chamber andthe filter.Inventive Concept 190. The apparatus according to Inventive Concept 187,wherein the apparatus further includes an elongate member configured topush at least a portion of the filter into the filter chamber.Inventive Concept 191. The apparatus according to Inventive Concept 187,wherein the plunger head is configured to push at least a portion of thefilter into the filter chamber.Inventive Concept 192. The apparatus according to Inventive Concept 187,wherein the testing device further includes a frangible seal thatremovably blocks liquid flow into the inlet of the filter chamber.Inventive Concept 193. The apparatus according to Inventive Concept 187,wherein the filter chamber is not disposed so as to receive the liquidthat is driven through at least one of the one or more valves.Inventive Concept 194. The apparatus according to Inventive Concept 187,wherein the filter chamber includes at least one of the one or morevalves, not disposed at the inlet of the filter chamber.Inventive Concept 195. The apparatus according to Inventive Concept 194,

wherein the liquid container is shaped so as to define one or moreopenings through a wall of the liquid container,

wherein the one or more openings are downstream of the filter when thefilter is removably disposed upstream of the filter chamber with thefilter partially covering the inlet of the filter chamber, and

wherein the filter chamber is not disposed so as to receive the liquidthat is driven through the one or more openings.

Inventive Concept 196. The apparatus according to Inventive Concept 173,wherein the filter is disposed at least partially within the filterchamber.Inventive Concept 197. The apparatus according to Inventive Concept 196,wherein the filter is disposed entirely within the filter chamber.Inventive Concept 198. The apparatus according to Inventive Concept 196,wherein the filter is shaped as a receptacle.Inventive Concept 199. The apparatus according to any one of InventiveConcepts 157-169, wherein the testing device further includes one ormore heating elements which are configured to heat the filter at agenerally constant temperature, the temperature in the range of 20 and50 degrees C.Inventive Concept 200. The apparatus according to Inventive Concept 199,wherein the temperature is in the range of 30 to 40 degrees C.Inventive Concept 201. The apparatus according to Inventive Concept 199,wherein the liquid container includes, upstream of the filter, afrangible dividing waterproof or water-resistant membrane that isolatesthe filter from the liquid in the liquid container.Inventive Concept 202. The apparatus according to Inventive Concept 199,wherein the one or more heating elements are disposed in the plunger.Inventive Concept 203. The apparatus according to any one of InventiveConcepts 157-169,

wherein the one or more valves are one or more first valves, and

wherein the testing device further includes one or more second pressurerelief valves, which are in fluid communication with the liquidcontainer and are disposed upstream of the filter.

Inventive Concept 204. The apparatus according to Inventive Concept 203,

wherein the testing device further includes a waste liquid receptacle,which is coupled to the liquid container downstream of the filter,

wherein the plunger is arranged to apply pressure to drive the liquidcontained in the liquid container through the filter and then into thewaste liquid receptacle, and

wherein the one or more second pressure relief valves are in fluidcommunication with the waste liquid receptacle not via the filter.

Inventive Concept 205. The apparatus according to Inventive Concept 203,

wherein the plunger includes a plunger shaft, and the plunger head isdisposed at a downstream end portion of the plunger shaft,

wherein the testing device includes one or more unfiltered liquidreceptacles, and

wherein the one or more second pressure relief valves are in fluidcommunication with the one or more unfiltered liquid receptacles.

Inventive Concept 206. The apparatus according to Inventive Concept 205,wherein the one or more unfiltered liquid receptacles are disposed alongthe plunger shaft.Inventive Concept 207. The apparatus according to Inventive Concept 206,wherein the one or more unfiltered liquid receptacles are removablycoupled to the plunger.Inventive Concept 208. The apparatus according to Inventive Concept 203,

wherein the one or more first valves include one or more firstpressure-activated valves configured to open upon exposure to a firstpressure gradient across the one or more first pressure-activatedvalves, and

wherein the one or more second pressure relief valves are configured toopen upon exposure to a second pressure gradient across the one or moresecond pressure relief valves, the second pressure gradient greater thanthe first pressure gradient.

Inventive Concept 209. The apparatus according to any one of InventiveConcepts 157-169, wherein the liquid container is shaped so as to defineupstream and downstream openings, and wherein an area of the upstreamopening is greater than the area of the downstream opening.Inventive Concept 210. The apparatus according to Inventive Concept 209,wherein the liquid container includes an upstream end portion thatincludes the upstream opening, and wherein the upstream end portion isconical.Inventive Concept 211. The apparatus according to Inventive Concept 210,wherein a diameter of the upstream opening is at least 10% greater thana diameter of the downstream opening.Inventive Concept 212. The apparatus according to any one of InventiveConcepts 157-169, wherein the apparatus further includes sterilepackaging, in which at least the at least the liquid container, the oneor more valves, and the filter are removably disposed.Inventive Concept 213. The apparatus according to any one of InventiveConcepts 157-169, wherein the apparatus further includes at least onecontainer containing an extraction reagent.Inventive Concept 214. The apparatus according to Inventive Concept 213,wherein the apparatus further includes a test strip.Inventive Concept 215. The apparatus according to any one of InventiveConcepts 157-169, wherein the apparatus further includes a containercontaining a solution for use in a detecting a pathogen.

There is further provided, in accordance with an Inventive Concept 216of the present invention, apparatus including a testing device fortesting for the presence of particulate in a liquid, the testing deviceincluding:

a liquid container for containing the liquid, wherein the liquidcontainer has an internal volume of between 0.5 and 500 ml;

one or more non-pressure-activated valves;

a filter, disposed in or downstream of the liquid container and upstreamof the one or more valves; and

a liquid-pressure source, which is arranged to apply pressure to drivethe liquid contained in the liquid container through the filter and thenthrough the one or more valves,

wherein the testing device is configured to automatically close the oneor more non-pressure-activated valves after the liquid-pressure sourceapplies the pressure to drive the liquid contained in the liquidcontainer through the filter and then through the one or morenon-pressure-activated valves.

Inventive Concept 217. The apparatus according to Inventive Concept 216,wherein the testing device is configured such that motion of theliquid-pressure source automatically closes the one or morenon-pressure-activated valves after the liquid-pressure source appliesthe pressure to drive the liquid contained in the liquid containerthrough the filter and then through the one or morenon-pressure-activated valves.Inventive Concept 218. The apparatus according to Inventive Concept 217,wherein the testing device is configured such that rotational motion ofthe liquid-pressure source automatically closes the one or morenon-pressure-activated valves after the liquid-pressure source appliesthe pressure to drive the liquid contained in the liquid containerthrough the filter and then through the one or morenon-pressure-activated valves.Inventive Concept 219. The apparatus according to Inventive Concept 218,

wherein the one or more non-pressure-activated valves include two discsthat are shaped so as to define respective sets of openings, and whereinthe one or more non-pressure-activated valves are configured to assumeopen and closed states when the two sets of openings are aligned andnon-aligned with each other, and

wherein the testing device is configured such that rotational motion ofthe liquid-pressure source automatically closes the one or morenon-pressure-activated valves by rotating at least one of the two discswith respect to the other of the discs, after the liquid-pressure sourceapplies the pressure to drive the liquid contained in the liquidcontainer through the filter and then through the one or morenon-pressure-activated valves.

There is further provided, in accordance with an Inventive Concept 220of the present invention, a method including:

-   -   incubating gargled fluid for between 12 and 75 hours in a        container that contains a liquid growth medium, a dehydrated        growth medium, or a gel growth medium; and

thereafter, performing a strep test using a rapid strep test (RST)technique on the gargled fluid and growth medium.

Inventive Concept 221. The method according to Inventive Concept 220,wherein performing the strep test using the RST technique includesperforming a lateral flow test.Inventive Concept 222. The method according to Inventive Concept 220,wherein performing the strep test using the RST technique includesperforming an RST technique selected from the group consisting of: anELISA-based RST, an antibody-coated-beads-based RST, anucleic-acid-based RST, and a fluorescent immunoassaying (FIA) RST.Inventive Concept 223. The method according to Inventive Concept 220,wherein performing the strep test using the RST technique includesperforming the RST technique on the gargled fluid and the growth mediumwhile the gargled fluid and the growth medium are in the container.Inventive Concept 224. The method according to Inventive Concept 220,wherein performing the strep test using the RST technique includestransferring at least a portion of the gargled fluid and the growthmedium to another container and performing the RST technique while theat least a portion of the gargled fluid and the growth medium are in theother container.Inventive Concept 225. The method according to Inventive Concept 224,wherein transferring the at least a portion of the gargled fluid and thegrowth medium to the other container includes:

inserting an absorbent element into the gargled fluid and growth medium;and

thereafter, placing the absorbent element into the other container.

Inventive Concept 226. The method according to Inventive Concept 225,wherein the absorbent element is a swab.Inventive Concept 227. The method according to Inventive Concept 226,wherein the swab is a flocked swab.Inventive Concept 228. The method according to Inventive Concept 224,wherein transferring the at least a portion of the gargled fluid and thegrowth medium includes transferring at least 0.05 ml of the gargledfluid and the growth medium.Inventive Concept 229. The method according to Inventive Concept 220,wherein performing the strep test using the RST technique furtherincludes filtering the gargled fluid and the growth medium afterincubating, and performing the strep test using the RST technique on thefilter.Inventive Concept 230. The method according to Inventive Concept 229,wherein filtering the gargled fluid and the growth medium afterincubating includes:

placing the gargled fluid and the growth medium in a liquid container ofa testing device; and

applying pressure to drive the gargled fluid and the growth mediumcontained in the liquid container (a) through a filter of the testingdevice and (b) then through one or more valves of the testing device,wherein the filter is disposed in or downstream of the liquid container,and wherein the one or more valves are disposed downstream of thefilter.

Inventive Concept 231. The method according to Inventive Concept 229,wherein filtering the gargled fluid and the growth medium afterincubating includes:

placing the gargled fluid and the growth medium in a liquid container ofa testing device;

applying pressure to drive the gargled fluid and the growth mediumcontained in the liquid container through a filter of the testingdevice, wherein the filter is disposed in or downstream of the liquidcontainer; and

thereafter, testing, within a filter chamber of the testing device, forthe presence of particulate trapped by the filter while the filter isdisposed at least partially in the filter chamber, wherein the filterchamber is (a) disposed downstream of the liquid container, (b) shapedso as to define an inlet, and (c) in fluid communication with thefilter.

There is further provided, in accordance with an Inventive Concept 232of the present invention, a method for testing for the presence ofparticulate in gargled fluid, the method including:

incubating the gargled fluid for between 12 and 75 hours in a containerthat contains a liquid growth medium, a dehydrated growth medium, or agel growth medium; and

thereafter, performing a test for the particulate using a rapid testtechnique on the gargled fluid and growth medium.

Inventive Concept 233. The method according to Inventive Concept 232,wherein performing the test using the rapid test technique includesperforming a lateral flow test.Inventive Concept 234. The method according to Inventive Concept 232,wherein performing the test using the rapid test technique includesperforming a rapid test technique selected from the group consisting of:an ELISA-based rapid test, an antibody-coated-beads-based rapid test, anucleic-acid-based rapid test, and a fluorescent immunoassaying (FIA)rapid test.

There is further provided, in accordance with an Inventive Concept 235of the present invention, a method for testing for the presence ofparticulate in gargled fluid, the method including:

incubating the gargled fluid for between 12 and 75 hours in a containerthat contains a liquid growth medium, a dehydrated growth medium, or agel growth medium; and

thereafter, performing a lateral flow test for the particulate on thegargled fluid and growth medium.

Inventive Concept 236. The method according to Inventive Concept 235,wherein the particulate is strep, and wherein performing the lateralflow test includes performing the lateral flow test for the strep.Inventive Concept 237. The method according to any one of InventiveConcepts 232 and 235, wherein performing the test includes performingthe test on the gargled fluid and the growth medium while the gargledfluid and the growth medium are in the container.Inventive Concept 238. The method according to any one of InventiveConcepts 232 and 235, wherein performing the test includes transferringat least a portion of the gargled fluid and the growth medium to anothercontainer and performing the test while the at least a portion of thegargled fluid and the growth medium are in the other container.Inventive Concept 239. The method according to any one of InventiveConcepts 220, 232, and 235, wherein the container does not contain agar.Inventive Concept 240. The method according to any one of InventiveConcepts 220, 232, and 235, further including mixing the gargled fluidwith the growth medium before incubating.

There is further provided, in accordance with an Inventive Concept 241of the present invention, a method including:

incubating saliva not swabbed from a patient's throat for between 12 and75 hours in a container that contains a liquid growth medium, adehydrated growth medium, or a gel growth medium; and

thereafter, performing a strep test using a rapid strep test (RST)technique on the saliva and growth medium.

Inventive Concept 242. The method according to Inventive Concept 241,wherein the saliva not swabbed from the throat of the patient is salivaspit by the patient.Inventive Concept 243. The method according to Inventive Concept 241,wherein the container does not contain agar.Inventive Concept 244. The method according to Inventive Concept 241,further including mixing the saliva with the growth medium beforeincubating.Inventive Concept 245. The method according to Inventive Concept 241,wherein performing the strep test using the RST technique includesperforming a lateral flow test.Inventive Concept 246. The method according to Inventive Concept 241,wherein performing the strep test using the RST technique includesperforming an RST technique selected from the group consisting of: anELISA-based RST, an antibody-coated-beads-based RST, anucleic-acid-based RST, and a fluorescent immunoassaying (FIA) RST.Inventive Concept 247. The method according to Inventive Concept 241,wherein incubating includes:

receiving, on an absorbent element, saliva from the patient's mouth; and

thereafter, placing the absorbent element into the container thatcontains the liquid growth medium, dehydrated growth medium, or gelgrowth medium.

Inventive Concept 248. The method according to Inventive Concept 247,wherein the absorbent element is a swab.Inventive Concept 249. The method according to Inventive Concept 248,wherein the swab is a flocked swab.Inventive Concept 250. The method according to Inventive Concept 247,wherein performing the strep test using the RST technique includesperforming the RST technique on the saliva and the growth medium whilethe saliva and the growth medium are in the container.Inventive Concept 251. The method according to Inventive Concept 247,wherein performing the strep test using the RST technique includestransferring at least a portion of the saliva and the growth medium toanother container and performing the RST technique while the at least aportion of the saliva and the growth medium are in the other container.Inventive Concept 252. The method according to Inventive Concept 251,wherein transferring the at least a portion of the saliva and the growthmedium to the other container includes:

removing the swab from the container that contains the liquid growthmedium, dehydrated growth medium, or gel growth medium; and

thereafter, placing the swab into the other container.

Inventive Concept 253. The method according to Inventive Concept 251,wherein transferring the at least a portion of the saliva and the growthmedium includes transferring at least 0.05 ml of the saliva and thegrowth medium.Inventive Concept 254. The method according to Inventive Concept 247,wherein performing the strep test using the RST technique furtherincludes filtering the at least a portion of the saliva and the growthmedium after incubating, and performing the strep test using the RSTtechnique on the filter.Inventive Concept 255. The method according to Inventive Concept 254,wherein filtering the saliva and the growth medium after incubatingincludes:

placing the saliva and the growth medium in a liquid container of atesting device; and

applying pressure to drive the saliva and the growth medium contained inthe liquid container (a) through a filter of the testing device and (b)then through one or more valves of the testing device, wherein thefilter is disposed in or downstream of the liquid container, and whereinthe one or more valves are disposed downstream of the filter.

Inventive Concept 256. The method according to Inventive Concept 254,wherein filtering the saliva and the growth medium after incubatingincludes:

placing the saliva and the growth medium in a liquid container of atesting device;

applying pressure to drive the saliva and the growth medium contained inthe liquid container through a filter of the testing device, wherein thefilter is disposed in or downstream of the liquid container; and

thereafter, testing, within a filter chamber of the testing device, forthe presence of particulate trapped by the filter while the filter isdisposed at least partially in the filter chamber, wherein the filterchamber is (a) disposed downstream of the liquid container, (b) shapedso as to define an inlet, and (c) in fluid communication with thefilter.

There is further provided, in accordance with an Inventive Concept 257of the present invention, a system including:

(a) a liquid including at least one substance selected from the group ofsubstances consisting of gargled fluid, saliva not swabbed from a throatof a patient, and an incubated culture medium containing a biologicalsample; and

(b) a testing device, which includes:

-   -   a liquid container containing the liquid;    -   one or more valves;    -   a filter, disposed in or downstream of the liquid container and        upstream of the one or more valves; and    -   a liquid-pressure source, which is arranged to apply pressure to        drive the liquid contained in the liquid container through the        filter and then through the one or more valves.        Inventive Concept 258. The system according to Inventive Concept        257, wherein the liquid includes the gargled fluid.        Inventive Concept 259. The system according to Inventive Concept        257, wherein the liquid includes the saliva not swabbed from the        throat of the patient.        Inventive Concept 260. The system according to Inventive Concept        257, wherein the liquid includes the incubated culture medium        containing the biological sample.        Inventive Concept 261. The system according to Inventive Concept        257, wherein the liquid container has an internal volume of        between 0.5 and 500 ml.        Inventive Concept 262. The system according to Inventive Concept        257, wherein the liquid-pressure source includes a plunger,        which includes a plunger head that is shaped so as to be        insertable into the liquid container.        Inventive Concept 263. The system according to Inventive Concept        257, wherein the liquid-pressure source includes a vacuum pump        disposed downstream of the one or more valves.        Inventive Concept 264. The system according to Inventive Concept        257, wherein the liquid-pressure source includes a        positive-pressure pump disposed upstream of the filter.        Inventive Concept 265. The system according to Inventive Concept        257, wherein the one or more valves include one or more        pressure-activated valves.        Inventive Concept 266. The system according to Inventive Concept        257, wherein the one or more valves include one or more        non-pressure-activated valves.        Inventive Concept 267. The system according to Inventive Concept        257, wherein the testing device further includes a waste liquid        receptacle, which is coupled to the liquid container downstream        of the one or more valves, and wherein the liquid-pressure        source is arranged to apply pressure to drive the liquid        contained in the liquid container through the filter, then        through the one or more valves, and then into the waste liquid        receptacle.        Inventive Concept 268. The system according to Inventive Concept        257, wherein the testing device further includes a filter        chamber that is (a) disposed downstream of the liquid        container, (b) shaped so as to define an inlet, and (c) in fluid        communication with the filter.

There is further provided, in accordance with an Inventive Concept 268of the present invention, apparatus including a testing device fortesting for the presence of particulate in a liquid, the testing deviceincluding:

(a) an upstream component, which includes:

-   -   (i) a plunger housing, which is shaped so as to define upstream        and downstream openings; and    -   (ii) a plunger, which includes a downstream plunger head that is        shaped so as to be insertable into the plunger housing so as to        form a movable seal with a wall of the plunger housing, wherein        an area of a downstream surface of the downstream plunger head        equals between 80% and 100% of an area of the downstream        opening; and

(b) a downstream component, which includes:

-   -   (i) a filter, which has a filter surface area of an upstream        side of the filter equal to at least 80% of the area of the        downstream surface of the downstream plunger head; and    -   (ii) a waste liquid receptacle, disposed downstream of the        filter,

wherein the testing device is shaped so as to define a liquid containerfor containing the liquid, and

wherein the upstream component and the downstream component areconfigured to be removably coupled together so as to form aliquid-impermeable seal.

Inventive Concept 270. The apparatus according to Inventive Concept 269,wherein the upstream component and the downstream component areconfigured to be removably coupled together so as to form theliquid-impermeable seal, such that the upstream component and thedownstream component partially overlap each other at an axial overlapregion that at least partially defines the liquid container.Inventive Concept 271. The apparatus according to Inventive Concept 269,wherein the testing device is configured such that at least 80% of thesurface area of an upstream side of the filter is exposed to outside thetesting device when the upstream component and the downstream componentare decoupled from each other.Inventive Concept 272. The apparatus according to Inventive Concept 269,wherein the upstream component and the downstream component areconfigured to be removably coupled together by click-fitting together.Inventive Concept 273. The apparatus according to Inventive Concept 269,wherein the upstream component and the downstream component areconfigured to be removably coupled together by friction-fittingtogether.Inventive Concept 274. The apparatus according to Inventive Concept 269,wherein the upstream component and the downstream component areconfigured to be removably coupled together by twist-and-lock fittingtogether.Inventive Concept 275. The apparatus according to any one of InventiveConcepts 269-274, wherein an area of the upstream opening is greaterthan the area of the downstream opening.Inventive Concept 276. The apparatus according to Inventive Concept 275,wherein the plunger housing includes an upstream end portion thatincludes the upstream opening, and wherein the upstream end portion isconical.Inventive Concept 277. The apparatus according to Inventive Concept 276,wherein a diameter of the upstream opening is at least 10% greater thana diameter of the downstream opening.

There is further provided, in accordance with an Inventive Concept 278of the present invention, a method including:

decoupling an upstream component of a testing device from a downstreamcomponent of the testing device so as to expose a filter of the testingdevice; and

testing for particulate trapped in the filter,

wherein the upstream component includes:

-   -   (i) a plunger housing, which is shaped so as to define upstream        and downstream openings; and    -   (ii) a plunger, which includes a downstream plunger head that is        shaped so as to be insertable into the plunger housing so as to        form a movable seal with a wall of the plunger housing, wherein        an area of a downstream surface of the downstream plunger head        equals between 80% and 100% of an area of the downstream        opening,

wherein the downstream component includes:

-   -   (i) the filter, wherein the filter has a filter surface area of        an upstream side of the filter equal to at least 80% of the area        of the downstream surface of the downstream plunger head; and    -   (ii) a waste liquid receptacle, disposed downstream of the        filter,

wherein the testing device is shaped so as to define a liquid containerfor containing a liquid that includes at least one substance selectedfrom the group of substances consisting of gargled fluid, saliva notswabbed from a throat of a patient, and an incubated culture mediumcontaining a biological sample, and

wherein the upstream component and the downstream component areconfigured to be removably coupled together so as to form aliquid-impermeable seal.

Inventive Concept 279. The method according to Inventive Concept 278,wherein the upstream component and the downstream component areconfigured to be removably coupled together so as to form theliquid-impermeable seal, such that the upstream component and thedownstream component partially overlap each other at an axial overlapregion that at least partially defines the liquid container.Inventive Concept 280. The method according to Inventive Concept 278,wherein the testing device is configured such that at least 80% of thesurface area of an upstream side of the filter is exposed to outside thetesting device when the upstream component and the downstream componentare decoupled from each other.Inventive Concept 281. The method according to Inventive Concept 278,wherein an area of the upstream opening is greater than the area of thedownstream opening.Inventive Concept 282. The method according to Inventive Concept 281,wherein the plunger housing includes an upstream end portion thatincludes the upstream opening, and wherein the upstream end portion isconical.Inventive Concept 283. The method according to Inventive Concept 282,wherein a diameter of the upstream opening is at least 10% greater thana diameter of the downstream opening.Inventive Concept 284. The method according to Inventive Concept 278,wherein the upstream component and the downstream component areconfigured to be removably coupled together by click-fitting together.Inventive Concept 285. The method according to Inventive Concept 278,wherein the upstream component and the downstream component areconfigured to be removably coupled together by friction-fittingtogether.Inventive Concept 286. The method according to Inventive Concept 278,wherein the upstream component and the downstream component areconfigured to be removably coupled together by twist-and-lock fittingtogether.

There is further provided, in accordance with an Inventive Concept 286of the present invention, apparatus including a testing device fortesting for the presence of particulate in a liquid, the testing deviceincluding:

a liquid container for containing the liquid;

a filter, disposed in or downstream of the liquid container; and

a plunger head, which (a) is shaped so as to be insertable into theliquid container, (b) is configured to apply pressure to drive theliquid from the liquid container through the filter, and (c) has adownstream surface that is at least partially coated with a solid orsemi-solid growth medium.

Inventive Concept 288. The apparatus according to Inventive Concept 287,wherein an area of the downstream surface of the plunger head is between0.3 and 100 cm2.Inventive Concept 289. The apparatus according to Inventive Concept 287,wherein the plunger head is shaped so as to be insertable into theliquid container so as to form a movable seal with a wall of the liquidcontainer.Inventive Concept 290. The apparatus according to Inventive Concept 287,wherein the testing device further includes a plunger shaft, and theplunger head is disposed at a downstream end portion of the plungershaft.Inventive Concept 291. The apparatus according to Inventive Concept 287,wherein the testing device further includes a waste liquid receptacle,coupled to the liquid container downstream of the filter.Inventive Concept 292. The apparatus according to any one of InventiveConcepts 287-291, wherein the growth medium includes agar.Inventive Concept 293. The apparatus according to any one of InventiveConcepts 287-291, wherein the growth medium is solid.Inventive Concept 294. The apparatus according to Inventive Concept 293,wherein the solid growth medium is dehydrated.Inventive Concept 295. The apparatus according to Inventive Concept 293,wherein the solid growth medium includes powdered solid growth medium.Inventive Concept 296. The apparatus according to any one of InventiveConcepts 287-291, further including a cap that is configured to becoupled to and fully cover the growth medium on the downstream surfaceof the plunger head.Inventive Concept 297. The apparatus according to Inventive Concept 296,wherein the cap is transparent.

There is further provided, in accordance with an Inventive Concept 297of the present invention, a method including:

pushing a plunger head to apply pressure to drive liquid from a liquidcontainer of a testing device through a filter of the testing device,wherein the plunger head has a downstream surface that is at leastpartially coated with a solid or semi-solid growth medium;

touching the downstream surface of the plunger head to the filter; and

assessing the downstream surface of the plunger head for biologicalgrowth.

Inventive Concept 299. The method according to Inventive Concept 298,wherein the liquid includes at least one substance selected from thegroup of substances consisting of gargled fluid, saliva not swabbed froma throat of a patient, and an incubated culture medium containing abiological sample.Inventive Concept 300. The method according to Inventive Concept 298,wherein assessing includes assessing the downstream surface of theplunger head for biological growth of a biological particulate selectedfrom the group consisting of: a microorganism, a fungus, a bacterium, aspore, a virus, a mite, a biological cell, a biological antigen, aprotein, a protein antigen, and a carbohydrate antigen.Inventive Concept 301. The method according to Inventive Concept 298,wherein the growth medium includes agar.Inventive Concept 302. The method according to Inventive Concept 298,wherein the method further includes heating the plunger head beforeassessing the downstream surface of the plunger head for biologicalgrowth.Inventive Concept 303. The method according to Inventive Concept 298,wherein the growth medium is solid.Inventive Concept 304. The method according to Inventive Concept 303,wherein the solid growth medium is dehydrated.Inventive Concept 305. The method according to Inventive Concept 303,wherein the solid growth medium includes powdered solid growth medium.Inventive Concept 306. The method according to Inventive Concept 298,further including coupling a cap the plunger head such that the capfully covers the growth medium on the downstream surface of the plungerhead.Inventive Concept 307. The method according to Inventive Concept 306,wherein the cap is transparent.

There is further provided, in accordance with an Inventive Concept 307of the present invention, a method including:

pushing a plunger head to apply pressure to drive liquid from a liquidcontainer of a testing device through a filter of the testing device;

touching a downstream surface of the plunger head to the filter;

thereafter, touching the downstream surface of the plunger head toculture medium contained in a culture-medium container;

heating the culture-medium container; and

assessing the culture-medium container for biological growth.

Inventive Concept 309. The method according to Inventive Concept 308,wherein the culture medium includes agar.Inventive Concept 310. The method according to Inventive Concept 308,wherein the liquid includes at least one substance selected from thegroup of substances consisting of gargled fluid, saliva not swabbed froma throat of a patient, and an incubated culture medium containing abiological sample.Inventive Concept 311. The method according to Inventive Concept 308,wherein assessing includes assessing the culture-medium container forbiological growth of a biological particulate selected from the groupconsisting of: a microorganism, a fungus, a bacterium, a spore, a virus,a mite, a biological cell, a biological antigen, a protein, a proteinantigen, and a carbohydrate antigen.Inventive Concept 312. The method according to Inventive Concept 308,wherein the downstream surface of the plunger head is rough.Inventive Concept 313. The method according to Inventive Concept 312,wherein touching the downstream surface of the plunger head to thefilter includes grinding the filter with the rough downstream surface.Inventive Concept 314. The method according to Inventive Concept 308,further including testing, within the testing device, for the presenceof a biological particulate trapped by the filter.

There is further provided, in accordance with an Inventive Concept 314of the present invention, a testing kit for testing for the presence ofparticulate in a liquid, the testing kit including:

a liquid container for containing the liquid, the liquid containershaped so as to define upstream and downstream openings;

a filter, disposed in or downstream of the liquid container; and

a plunger head that (a) is shaped so as to be insertable into the liquidcontainer so as to form a movable seal with a wall of the liquidcontainer, and (b) is arranged such that when pushed, the plunger headapplies pressure to drive the liquid contained in the liquid containerthrough the filter and then through the downstream opening,

wherein the testing kit does not include a plunger shaft.

Inventive Concept 316. The testing kit according to Inventive Concept315, wherein the filter is configured to trap at least 40% of group Astreptococcus bacteria and allow passage of the liquid.Inventive Concept 317. The testing kit according to Inventive Concept315, wherein the filter is configured to trap at least 40% of aparticulate to be tested and allow passage of the liquid.Inventive Concept 318. The testing kit according to Inventive Concept315, further including sterile packaging, in which at least the liquidcontainer, plunger head, and the filter are removably disposed.Inventive Concept 319. The testing kit according to Inventive Concept315, wherein the liquid container includes a liquid-tight seal disposeddownstream of the filter, and wherein the testing kit is arranged suchthat when the plunger head is pushed, the plunger head applies thepressure to break or open the seal and drive the liquid through thefilter and then through the downstream opening.

There is further provided, in accordance with an Inventive Concept 319of the present invention, a method including:

receiving a testing kit including (a) a liquid container, the liquidcontainer shaped so as to define upstream and downstream openings, (b) afilter, disposed in or downstream of the liquid container, (c) and aplunger head;

coupling the plunger head to a plunger shaft;

receiving a liquid in the liquid container;

inserting the plunger head into the liquid container so as to form amovable seal with a wall of the liquid container; and

using the plunger shaft, pushing the plunger head to apply pressure todrive the liquid contained in the liquid container through the filterand then through the downstream opening,

wherein the testing kit does not include the plunger shaft.

Inventive Concept 321. The method according to Inventive Concept 320,further including, after pushing the plunger head, testing for thepresence of particulate trapped by the filter.

There is further provided, in accordance with an Inventive Concept 322of the present invention, a method for testing for the presence of groupA streptococcus bacteria in a sample of oral fluid obtained from apatient, the method including:

generating a biological product by incubating the sample of oral fluidfor between 12 and 50 hours in a container that contains a liquid growthmedium, the liquid growth medium having (a) a total nitrogen sourceconcentration between 75 and 300 g/L and (b) a total solidsconcentration between 92.5 and 370 g/L; and

thereafter, performing a strep test using a rapid strep test (RST)technique on the biological product.

Inventive Concept 323. The method according to Inventive Concept 322,wherein incubating includes incubating for between 16 and 50 hours.Inventive Concept 324. The method according to Inventive Concept 322,wherein the container does not contain agar.Inventive Concept 325. The method according to Inventive Concept 322,wherein performing the strep test using the RST technique includesperforming a lateral flow test.Inventive Concept 326. The method according to Inventive Concept 322,wherein performing the strep test using the RST technique includesperforming an RST technique selected from the group consisting of: anELISA-based RST, an antibody-coated-beads-based RST, anucleic-acid-based RST, and a fluorescent immunoassaying (FIA) RST.Inventive Concept 327. The method according to Inventive Concept 322,wherein the liquid growth medium has a pH of between 6 and 8.3.Inventive Concept 328. The method according to Inventive Concept 322,wherein incubating includes incubating for between 12 and 36 hours.Inventive Concept 329. The method according to any one of InventiveConcepts 322-328, wherein the sample of oral fluid is selected from thegroup consisting of: gargled fluid gargled by the patient, and salivanot swabbed from a throat of the patient.Inventive Concept 330. The method according to Inventive Concept 329,wherein the sample of oral fluid is the gargled fluid.Inventive Concept 331. The method according to Inventive Concept 329,wherein the sample of oral fluid is the saliva not swabbed from thethroat of the patient.Inventive Concept 332. The method according to Inventive Concept 331,wherein the saliva not swabbed from the throat of the patient is salivaspit by the patient.Inventive Concept 333. The method according to any one of InventiveConcepts 322-328, wherein the sample of oral fluid is saliva swabbedfrom a tonsil of the patient.Inventive Concept 334. The method according to any one of InventiveConcepts 322-328, wherein the liquid growth medium has a total sugarconcentration of between 7 g/L and 20 g/L.Inventive Concept 335. The method according to Inventive Concept 334,wherein the total sugar concentration is between 7 g/L and 14 g/L.Inventive Concept 336. The method according to Inventive Concept 334,wherein the liquid growth medium has a glucose concentration of between8 g/L and 12 g/L.Inventive Concept 337. The method according to Inventive Concept 336,wherein the glucose concentration is between 8.5 g/L and 9.5 g/L.Inventive Concept 338. The method according to any one of InventiveConcepts 322-328, wherein the total nitrogen source concentration isbetween 105 and 180 g/L.Inventive Concept 339. The method according to Inventive Concept 338,wherein the total nitrogen source concentration is between 120 and 160g/L.Inventive Concept 340. The method according to any one of InventiveConcepts 322-328, wherein the total solids concentration is between 130and 222 g/L.Inventive Concept 341. The method according to Inventive Concept 340,wherein the total solids concentration is between 148 and 193 g/L.Inventive Concept 342. The method according to any one of InventiveConcepts 322-328, wherein performing the strep test includes applyingone or more extraction reagents to the biological product.Inventive Concept 343. The method according to any one of InventiveConcepts 322-328, wherein generating the biological product furtherincludes filtering the sample of oral fluid and the liquid growth mediumafter incubating.Inventive Concept 344. The method according to Inventive Concept 343,wherein performing the strep test using the RST technique includesperforming the strep test using the RST technique on the filter.Inventive Concept 345. The method according to Inventive Concept 343,wherein performing the strep test includes applying one or moreextraction reagents to the filtered biological product.

There is further provided, in accordance with an Inventive Concept 345of the present invention, a liquid growth medium having (a) a totalnitrogen source concentration between 75 and 300 g/L and (b) a totalsolids concentration between 92.5 and 370 g/L.

Inventive Concept 347. The liquid growth medium according to InventiveConcept 346, wherein the liquid growth medium has a pH of between 6 and8.3.Inventive Concept 348. The liquid growth medium according to InventiveConcept 346, wherein the liquid growth medium has a total sugarconcentration of between 7 g/L and 20 g/L.Inventive Concept 349. The liquid growth medium according to InventiveConcept 348, wherein the total sugar concentration is between 7 g/L and14 g/L.Inventive Concept 350. The liquid growth medium according to InventiveConcept 348, wherein the liquid growth medium has a glucoseconcentration of between 8 g/L and 12 g/L.Inventive Concept 351. The liquid growth medium according to InventiveConcept 350, wherein the glucose concentration is between 8.5 g/L and9.5 g/L 352. The liquid growth medium according to Inventive Concept346, wherein the total nitrogen source concentration is between 105 and180 g/L.Inventive Concept 353. The liquid growth medium according to InventiveConcept 352, wherein the total nitrogen source concentration is between120 and 160 g/L.Inventive Concept 354. The liquid growth medium according to InventiveConcept 346, wherein the total solids concentration is between 130 and222 g/L.Inventive Concept 355. The liquid growth medium according to InventiveConcept 354, wherein the total solids concentration is between 148 and193 g/L.Inventive Concept 356. An assembly including the liquid growth mediumaccording to any one of Inventive Concepts 346-355, the assembly furtherincluding a sealed sterile container that contains the liquid growthmedium.Inventive Concept 357. An assembly including the liquid growth mediumaccording to any one of Inventive Concepts 346-355, the assembly furtherincluding a container that contains the liquid growth medium and asample of oral fluid obtained from a patient.Inventive Concept 358. A kit including the liquid growth mediumaccording to any one of Inventive Concepts 346-355, the kit furtherincluding a lateral flow strep test strip.Inventive Concept 359. A kit including the liquid growth mediumaccording to any one of Inventive Concepts 346-355, the kit furtherincluding one or more extraction reagents.Inventive Concept 360. A kit including the liquid growth mediumaccording to any one of Inventive Concepts 346-355, the kit furtherincluding a filter.

There is further provided, in accordance with an Inventive Concept 361of the present invention, a method of preparing a liquid growth medium,the method including:

adding a quantity of powdered growth medium to a volume of distilledwater; and

stirring until the powdered growth medium is dissolved in the distilledwater to produce the liquid growth medium,

wherein the quantity of powdered growth medium and the volume of thedistilled water are selected such that the liquid growth medium has (a)a total nitrogen source concentration between 75 and 300 g/L and (b) atotal solids concentration between 92.5 and 370 g/L.

Inventive Concept 362. The method according to Inventive Concept 361,wherein the liquid growth medium has a pH of between 6 and 8.3.Inventive Concept 363. The method according to Inventive Concept 361,wherein the quantity of powdered growth medium and the volume of thedistilled water are selected such that the liquid growth medium has atotal sugar concentration of between 7 g/L and 20 g/L.Inventive Concept 364. The method according to Inventive Concept 363,wherein the quantity of powdered growth medium and the volume of thedistilled water are selected such that the total sugar concentration isbetween 7 g/L and 14 g.Inventive Concept 365. The method according to Inventive Concept 363,wherein the quantity of powdered growth medium and the volume of thedistilled water are selected such that the liquid growth medium has aglucose concentration of between 8 g/L and 12 g/L.Inventive Concept 366. The method according to Inventive Concept 365,wherein the quantity of powdered growth medium and the volume of thedistilled water are selected such that the glucose concentration isbetween 8.5 g/L and 9.5 g/L.Inventive Concept 367. The method according to Inventive Concept 361,wherein the quantity of powdered growth medium and the volume of thedistilled water are selected such that the total nitrogen sourceconcentration is between 105 and 180 g/L.Inventive Concept 368. The method according to Inventive Concept 367,wherein the quantity of powdered growth medium and the volume of thedistilled water are selected such that the total nitrogen sourceconcentration is between 120 and 160 g/L.Inventive Concept 369. The method according to Inventive Concept 361,wherein the quantity of powdered growth medium and the volume of thedistilled water are selected such that the total solids concentration isbetween 130 and 222 g/L.Inventive Concept 370. The method according to Inventive Concept 369,wherein the quantity of powdered growth medium and the volume of thedistilled water are selected such that the total solids concentration isbetween 148 and 193 g/L.

The present invention will be more fully understood from the followingdetailed description of embodiments thereof, taken together with thedrawings, in which:

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A-H are schematic illustrations of a testing device for testingfor presence of particulate in a liquid, in accordance with anapplication of the present invention;

FIG. 2 is a schematic illustration of another testing device for testingfor presence of particulate in a liquid, in accordance with anapplication of the present invention;

FIGS. 3A-B are schematic illustrations of yet another testing device fortesting for presence of particulate in a liquid, in accordance with anapplication of the present invention;

FIG. 3C is a schematic illustration of still another testing device fortesting for presence of particulate in a liquid, in accordance with anapplication of the present invention;

FIGS. 4A-C are schematic illustrations of another testing device fortesting for presence of particulate in a liquid, in accordance with anapplication of the present invention;

FIGS. 5A-B are schematic illustrations of additional testing devices fortesting for presence of particulate in a liquid, in accordance withrespective applications of the present invention;

FIGS. 6A-C are schematic illustrations of yet another testing device fortesting for presence of particulate in a liquid, in accordance with anapplication of the present invention;

FIGS. 7A-C and 8A-E are schematic illustrations of still another testingdevice for testing for presence of particulate in a liquid, inaccordance with an application of the present invention;

FIG. 9 is a schematic illustration of another testing device for testingfor presence of particulate in a liquid, in accordance with anapplication of the present invention;

FIGS. 10A-C are schematic illustrations of yet another testing devicefor testing for presence of particulate in a liquid, in accordance withan application of the present invention;

FIGS. 10D-K are schematic illustrations of a testing device for testingfor presence of particulate in a liquid, in accordance with anapplication of the present invention;

FIGS. 10L-M are schematic illustrations of a testing device for testingfor presence of particulate in a liquid, in accordance with anapplication of the present invention;

FIGS. 10N-O are schematic illustrations of a testing device for testingfor presence of particulate in a liquid, in accordance with anapplication of the present invention;

FIGS. 10P-Q are schematic illustrations of a testing device for testingfor presence of particulate in a liquid, in accordance with anapplication of the present invention;

FIGS. 11A-E are schematic illustrations of the testing device of FIGS.1A-H further comprising one or more heating elements, in accordance withrespective applications of the present invention;

FIG. 12 is a schematic illustration of a method for performing a test,in accordance with an application of the present invention;

FIGS. 13A-B are schematic illustrations of a method for performing abackup test, in accordance with an application of the present invention;

FIG. 13C is a schematic illustration of another method for performing abackup test, in accordance with an application of the present invention;

FIG. 13D is a flowchart depicting a method for performing a backup streptest using rapid strep test (RST) techniques on gargled fluid afterincubation, in accordance with some applications of the presentinvention;

FIG. 13E is a flowchart depicting a method for performing a backup streptest using rapid strep test (RST) techniques on saliva not swabbed froma patient's throat after incubation, in accordance with someapplications of the present invention;

FIGS. 14A-C are schematic illustrations of another testing device fortesting for presence of particulate in a liquid, in accordance with anapplication of the present invention;

FIGS. 15A-C are schematic illustrations of a method for using thetesting device of FIGS. 14A-C for testing for presence of particulate ina liquid, in accordance with an application of the present invention;

FIGS. 16A-B are schematic illustrations of a testing system, inaccordance with an application of the present invention;

FIG. 17 is a schematic exploded view of a testing device of the testingsystem of FIG. 16A-B, in accordance with an application of the presentinvention;

FIGS. 18A-F are schematic illustrations of a method for using thetesting system of FIGS. 16A-B to test for the presence of theparticulate in a liquid, in accordance with an application of thepresent invention;

FIGS. 19A-D, 20, 21, and 22 are tables that present results of anexperiment conducted in accordance with an application of the presentinvention;

FIGS. 23, 24, 25, 26, and 27 are tables that present results of anotherexperiment conducted in accordance with an application of the presentinvention; and

FIGS. 28 and 29 are graphs that present results of experiments conductedin accordance with respective applications of the present invention.

DETAILED DESCRIPTION OF APPLICATIONS

FIGS. 1A-H are schematic illustrations of a testing device 20 fortesting for presence of particulate in a liquid 22, in accordance withan application of the present invention. For some applications, theparticulate comprises biological particulate, for example, amicroorganism, a fungus, a bacterium (e.g., a group A streptococcusbacterium), a spore, a virus, a mite, a biological cell, a biologicalantigen, a protein, a protein antigen, and a carbohydrate antigen.Alternatively, testing device 20 is used for testing a non-particulatesubstance of interest, whether a biological or chemical substance,soluble, immiscible or an emulsion, an atom, a molecule, a polymer or amixture of substances.

Testing device 20 typically comprises:

-   -   a liquid container 30 for containing liquid 22; typically,        liquid container 30 has an internal volume of at least 0.5 ml        (e.g., at least 1 ml, such as at least 5 ml), no more than 500        ml (e.g., no more than 70 ml), and/or between 0.5 ml (e.g., 1 ml        or 5 ml) and 500 ml (e.g., 70 ml);    -   a filter 32, disposed in or downstream of liquid container 30;        and    -   a liquid-pressure source 34, which is arranged to apply pressure        to drive liquid 22 contained in liquid container 30 through        filter 32.

As used in the present application, including in the claims, “upstream”and “downstream” refer to the direction of fluid flow through testingdevice 20, and not the orientation of the device with respect to theEarth. For example, filter chamber 736, described hereinbelow withreference to FIGS. 7A-8E, is downstream of liquid container 730, eventhough the filter chamber is physically above the liquid container whenthe testing device is oriented as shown in the figures.

Typically, liquid container 30 does not comprise a Luer lock or anyother type of needle-coupling mechanism.

Filter 32 comprises synthetic or natural materials formed, for example,as a matrix, membrane, fabric, beads, or other configuration. Forexample, the inventors have tested the following filters manufactured bySterlitech (Washington, USA):

-   -   Grade C glass microfiber filter media (Cat. No. C2500 & C3700)    -   GC-50 glass fiber membrane filters (Cat. No. GC5037100)    -   polyethersulfone (PES) membrane filters (Cat. No. PES0825100,        PES0837100, PES1225100, PES1237100, PES06525100, PES4525100,        PES4525100)    -   polycarbonate membrane filters (Cat. No. PCT0613100, PCT2025100,        PCT0625100, PCT1025100, PCT0825100)    -   cellulose acetate membrane filters (Cat. No. CA0825100)    -   polyester membrane filters (Cat. No. PET0125100, PET0825100)

Typically, filter 32 is configured to trap at least 40% (such as atleast 95%, e.g., at least 99%) of the particulate to be tested and allowpassage of liquid 22. For example, for applications in which theparticulate is group A streptococcus bacteria, the filter may beconfigured to trap at least 40% (such as at least 95%, e.g., at least99%) of the group A streptococcus bacteria and allow passage of liquid22. For some applications, filter 32 has a filter surface area of anupstream side of the filter equal to at least 0.3 cm2, no more than 100cm2 (e.g., no more than 30 cm2), and/or between 0.3 cm2 and 100 cm2,such as between 0.3 and 30 cm2.

For some applications, liquid-pressure source 34 comprises at least oneof the following:

-   -   a plunger 40, which comprises a plunger head 42 that is shaped        so as to be insertable into liquid container 30 so as to form a        movable seal with a wall of a plunger housing (optionally, all        or a portion of liquid container 30 defines the wall of the        plunger housing);    -   a positive-pressure pump (e.g., a hydraulic pump, a syringe, or        a motorized and/or electrical pump) disposed upstream of filter        32 (configuration not shown);    -   optionally, for some application, the positive-pressure pump        comprises a chamber with one or more flexible walls, the        squeezing of which pumps air and/or liquid 22 itself out of the        chamber; or    -   a vacuum pump disposed downstream of filter 32 (and, if        provided, of the one or more valves 60, described hereinbelow)        (configuration not shown).

For some applications, plunger 40 further comprises a plunger shaft, andplunger head 42 is disposed at a downstream end portion of the plungershaft. Typically, but not necessarily, plunger 40 has one of thefollowing configurations:

-   -   the plunger head comprises a separate piece of material (e.g.,        comprising a polymer) that is coupled to the plunger shaft and        is shaped so as to define the downstream surface of plunger head        42 and optionally a lateral sealing surface, or    -   the distal surface of plunger head 42 is defined by the end of        the plunger shaft, and, for example, a separate sealing ring        (e.g., comprising a polymer) may be provided to provide a        lateral sealing surface.

For some applications, testing device 20 further comprises a wasteliquid receptacle 46, which is coupled to liquid container 30 downstreamof filter 32 (and, if provided, of the one or more valves 60, describedhereinbelow). Liquid-pressure source 34 is arranged to apply pressure todrive liquid 22 contained in liquid container 30 through filter 32 andthen into waste liquid receptacle 46.

For some applications, testing device 20 further comprises a filterchamber 36 that is (a) disposed downstream of liquid container 30, (b)shaped so as to define an inlet 38, and (c) in fluid communication withfilter 32. Filter chamber 36 is shaped such that when filter 32 ispushed into the filter chamber, such as described hereinbelow withreference to

FIGS. 1D-E, the filter chamber collects filter 32 into a relativelysmall volume, thereby increasing the consolidated sensitivity of rapidand backup tests for particulate trapped by filter 32. If, by contrast,filter 32 were flat in liquid container 30, it would be difficult tocollect a sample from a high percentage of the surface of the filter. Inaddition, filter chamber 36 readily hosts at least one extractionreagent 86 and a test strip 88, as described hereinbelow with referenceto FIGS. 1G-H.

Optionally, filter chamber 36 is nipple-shaped. For some applications inwhich testing device 20 comprises waste liquid receptacle 46, filterchamber 36 is laterally surrounded by at least a portion of waste liquidreceptacle 46, such as shown in FIGS. 1A-H. Alternatively oradditionally, for some applications, filter chamber 36 is disposedwithin waste liquid receptacle 46, such as shown in FIGS. 1A-H.

For some applications, inlet 38 of filter chamber 36 has an inlet areathat equals at least 4%, no more than 40%, and/or between 4% and 40% ofa filter surface area of an upstream side of filter 32, such as between10% and 20%. Alternatively or additionally, for some applications,filter chamber 36 has:

-   -   an internal volume of at least 0.5 ml, no more than 12 ml (e.g.,        no more than 4 ml), and/or between 0.5 and 12 ml (such as        between 0.5 and 4 ml), such as at least 1 ml (e.g., at least 2        ml), no more than 5 ml, and/or between 1 and 5 ml, such as        between 2 and 5 ml,    -   an internal surface area that equals at least 10%, no more than        150%, and/or between 10% and 150% of a filter surface area of an        upstream side of filter 32, such as between 70% and 130%,    -   an internal length L equal to between 0.5 and 10 cm, such as        between 1.5 and 5 CM,    -   an internal width W equal to between 0.3 and 3 cm, such as        between 0.5 and 1.5 CM,    -   an internal length L of at least 0.5 cm, no more than 10 cm        (e.g., no more than 5 cm), and/or between 0.5 and 10 cm, such as        between 0.5 cm and 5 cm, e.g., between 1 and 5 cm, and/or    -   an internal length L equal to at least 50%, no more than 2000%,        and/or between 50% and 2000% of a greatest internal width W of        filter chamber 36, such as between 200% and 600%.

For some applications, such as shown in FIGS. 1A-H, filter chamber 36comprises one or more pressure-activated valves 50, not disposed atinlet 38. For applications in which testing device 20 comprises wasteliquid receptacle 46, the one or more pressure-activated valves 50 aretypically disposed in fluid communication between filter chamber 36 andwaste liquid receptacle 46. For some applications, liquid container 30is shaped so as to define one or more openings 51 (typically, non-valvedopenings) through a wall of liquid container 30, the one or moreopenings 51 are downstream of filter 32 when filter 32 is removablydisposed upstream of filter chamber 36 with filter 32 partially coveringinlet 38, and filter chamber 36 is not disposed so as to receive liquid22 that is driven through the one or more openings 51. The one or moreopenings 51 allow liquid 22 to pass, thereby drawing the liquid throughfilter 32. (As described hereinabove with reference to FIGS. 1A-B,testing device 20 may comprise an upstream component 70 and a downstreamcomponent 72 that are removably coupled together; in suchconfigurations, the one or more openings 51 defined by liquid container30 may optionally be defined by the portion of downstream component 72that helps define liquid container 30.)

For some applications, such as shown in FIGS. 1A-D, filter 32 isremovably disposed upstream of filter chamber 36 with filter 32partially covering inlet 38. For some applications, inlet 38 has aninlet centroid 52 that is disposed within a distance of a filtercentroid 54, the distance equal to 50% of a greatest dimension of filter32, when filter 32 is removably disposed upstream of filter chamber 36with filter 32 partially covering inlet 38. For example, filter 32 maybe centered upstream of inlet 38.

For some applications, an elongate member 56 is provided that configuredto push at least a portion of filter 32 into filter chamber 36.Optionally, elongate member 56 comprises a swab 58 at a distal end ofthe elongate member. In applications in which filter chamber 36comprises one or more pressure-activated valves 50, inserting elongatemember 56 into filter chamber may squeeze any liquid 22 remaining infilter chamber 36 through one or more pressure-activated valves 50 andout of filter chamber 36. For other applications in whichliquid-pressure source 34 comprises plunger 40, plunger head 42 isconfigured to push at least a portion of filter 32 into filter chamber36 (configuration not shown). In applications in which filter chamber 36comprises one or more pressure-activated valves 50, inserting plungerhead 42 into filter chamber may squeeze any liquid 22 remaining infilter chamber 36 through one or more pressure-activated valves 50 andout of filter chamber 36.

Reference is still made to FIGS. 1A-H. In an application of the presentinvention, testing device 20 further comprises one or more valves 60.For these applications, filter 32 is typically disposed in or downstreamof liquid container 30 and upstream of the one or more valves 60.Liquid-pressure source 34 is arranged to apply pressure to drive liquid22 contained in liquid container 30 through filter 32 and then throughthe one or more valves 60. For applications in which testing device 20comprises waste liquid receptacle 46, waste liquid receptacle 46 istypically coupled (removably or permanently) to liquid container 30downstream of the one or more valves 60, and liquid-pressure source 34is arranged to apply pressure to drive liquid 22 contained in liquidcontainer 30 through filter 32, then through the one or more valves 60,and then into waste liquid receptacle 46. Typically filter chamber 36 isnot disposed so as to receive liquid 22 that is driven through at leastone of the one or more valves 60.

For some applications, the one or more valves 60 comprise one or morepressure-activated valves. For example, as mentioned above, filterchamber 36 may comprise one or more pressure-activated valves 50, notdisposed at inlet 38. For example, the pressure-activated valves may beformed from slits or flaps in an elastic material (such as silicone), ormay comprise any small valves known in the valve art. The one or morepressure-activated valves are configured to open at the higher pressureapplied by liquid-pressure source 34, so as to allow liquid 22 to passthrough filter 32, and to remain closed at the much lower pressureapplied by at least one extraction reagent 86, as described hereinbelowwith reference to FIGS. 1G-H. Preventing the leakage of the at least oneextraction reagent 86 causes the at least one extraction reagent 86 tobathe filter 32, which is beneficial for optimal testing for particulatetrapped by filter 32 using a test strip 88, also as describedhereinbelow with reference to FIGS. 1G-H.

Alternatively or additionally, for some applications, the one or morevalves 60 comprise one or more non-pressure-activated valves, such asdescribed hereinbelow with reference to FIGS. 10A-C, 10D-K, 10L-M,10N-0, and/or 10P-Q.

For some applications, sterile packaging is provided, in which at leastliquid container 30, filter chamber 36, the one or more valves 60,and/or filter 32 are removably disposed. The sterile packaging comprisesone or more sterile packages; for example, each element may be removablydisposed in a separate one of the packages, and/or more than one theelements may be disposed in a single one of the packages.

For some applications, at least one container comprising the at leastone extraction reagent 86 is provided. For example, the at least oneextraction reagent 86 may comprise 2M sodium nitrite and/or 0.2M aceticacid, and/or a releasing agent, which, upon contacting a microorganism,releases an antigen from the microorganism. For applications in whichmore than one extraction reagent 86 is provided, and/or extractionreagent 86 comprises a plurality of substances, each of the extractionreagents 86 and/or substances may be provided in a separate container,and the extraction reagents 86 and/or substances are combined prior to(e.g., immediately prior to) performing the assay. Alternatively oradditionally, for some applications, a test strip 88 is provided.Typically, test strip 88 is a lateral flow test strip, such as a lateralflow immunoassay (e.g., chromatographic immunoassay) test strip, as isknown in the art. For example, test strip 88 may contain an antibodyspecific to strep A carbohydrate antigen, and the mixture migrates upthe test strip and reacts with the antibody, thus generating a line onthe test strip; the presence of this line indicates a positive testresult. Alternatively or additionally, for some applications, acontainer is provided containing a solution for use in a detecting apathogen.

Reference is still made to FIGS. 1A-H. In an application of the presentinvention, testing device 20 comprises an upstream component 70 and adownstream component 72 (labeled in FIGS. 1B and 1C).

Upstream component 70 typically comprises:

-   -   a plunger housing 74, which is shaped so as to define an        upstream opening 76 (labeled in FIG. 1B) and a downstream        opening 78 (labeled in FIG. 1C); and    -   plunger 40, which comprises a downstream plunger head 42 that is        shaped so as to be insertable into plunger housing 74 so as to        form a movable seal with a wall of plunger housing 74;        typically, an area of a downstream surface 80 of downstream        plunger head 42 equals between 80% and 100% of an area of        downstream opening 78 (unlike in conventional syringes, in which        the downstream surface of the plunger head is typically much        larger than the narrow downstream opening of the syringe        barrel).

Typically, plunger housing 74 does not comprise a Luer lock or any othertype of needle-coupling mechanism.

Downstream component 72 typically comprises:

-   -   filter 32, which has a filter surface area if an upstream side        of the filter equal to at least 80% of the area of downstream        surface 80 of the downstream plunger head 42;    -   waste liquid receptacle 46, disposed downstream of filter 32;        and    -   for applications in which it is provide, filter chamber 36.

Testing device 20 is shaped so as to define liquid container 30 forcontaining liquid 22. Upstream component 70 and downstream component 72are configured to be removably coupled together so as to form aliquid-impermeable seal, as shown in FIGS. 1A and 1B. FIG. 1C showsupstream component 70 and downstream component 72 after they have beendecoupled from each other. For example, upstream component 70 anddownstream component 72 may be configured to be removably coupledtogether by click-fitting together, by friction-fitting together, bytwist-and-lock fitting together, or by magnetic coupling together.

For some applications, such as shown in FIGS. 1A-B, upstream component70 and downstream component 72 are configured to be removably coupledtogether so as to form the liquid-impermeable seal, such that upstreamcomponent 70 and downstream component 72 partially overlap each other atan axial overlap region 82 (labeled in FIG. 1B) that at least partiallydefines liquid container 30. For other applications, upstream component70 and downstream component 72 do not axially overlap (configuration notshown); in these other applications, liquid container 30 is optionallydefined only by downstream component 72 and not by upstream component70. For some applications, as perhaps best shown in the blow-up in FIG.1A, an outer edge of filter 32 is squeezed directly or indirectlybetween upstream component 70 and downstream component 72 to hold thefilter in place until upstream component 70 is decoupled from downstreamcomponent 72.

In general, in all of the configurations of testing devices describedherein that comprise upstream and downstream components that areremovably coupled together, the liquid container may be defined in partby the upstream component and in part by the downstream component. Forexample, a distal downstream wall of the liquid container that supportsthe filter may be defined by the downstream component, while the lateralwall of the liquid container may be defined by the upstream component orby the upstream and downstream components in combination.

For some applications, such as shown in FIGS. 1C-D, testing device 20 isconfigured such that at least 80% of the surface area of an upstreamside of filter 32 is exposed to outside testing device 20 when upstreamcomponent 70 and downstream component 72 are decoupled from each other.

For some applications, an area of upstream opening 76 is greater thanthe area of downstream opening 78. For example, a diameter of upstreamopening 76 may be at least 10% (e.g., 20%, such as 30%) greater than adiameter of downstream opening 78. For some of these applications,plunger housing 74 includes an upstream end portion 84 (labeled in FIG.1B) that includes upstream opening 76, and upstream end portion 84 isconical and/or funnel-shaped.

Reference is still made to FIGS. 1A-H. In an application of the presentinvention, a method is provided for testing liquid 22 for the presenceof the particulate. For some applications, the particulate comprisesbiological particulate, for example, a microorganism, a fungus, abacterium, a spore, a virus, a mite, a biological cell, a biologicalantigen, a protein, a protein antigen, and a carbohydrate antigen.

For applications in which one or more components of testing device 20are removably disposed in sterile packing, the one or more componentsare removed from the sterile packaging.

As shown in FIG. 1A, the method comprises receiving, in liquid container30, liquid 22 from a patient's mouth. For some applications, liquid 22comprises gargled fluid, i.e., a gargle fluid that the patient hasgargled in his or her mouth and spit out, perhaps along with somesaliva. In the present application, including in the claims, “gargledfluid” means “gargle fluid” that has been gargled by a patient.Typically, the gargle fluid includes water, carbonated water, saline(e.g., phosphate buffered saline), Pelargonium sidoides extract, tannicacid, balloon flower Platycodon grandiflorus, berberine sulfate,S-carboxymethylcysteine, curcumin, coloring, flavoring, a detergent(such as Polysorbate 20 (e.g., Tween® 20)), or any combination thereof.In some applications, the gargle fluid is carbonated. Alternatively oradditionally, for some applications, a detergent, such as Polysorbate 20(e.g., Tween® 20) is added to the gargled fluid after being gargled bythe patient. Alternatively, liquid 22 may comprise another type ofbiological fluid, such as blood (e.g., diluted blood), urine, stool(e.g., diluted stool), gastrointestinal (GI) fluid, or bronchoalveolarlavage fluid.

Alternatively, liquid 22 comprises saliva not swabbed from the throat ofa patient (i.e., the saliva was collected without swabbing the patient'sthroat). (The distinction between “swab” as a verb and as a noun isnoted. A “swab” (as a noun) may be used to obtain saliva without“swabbing” (as a verb) the patient's throat. For example, the patientmay suck on a swab, or a swab may be dipped in a container into whichgargle fluid or saliva has been placed.) By contrast, incommonly-practiced techniques for testing for strep, the tonsils areswabbed. Further alternatively, liquid 22 comprises liquid from acultured medium containing a biological sample which had been incubatedwithin the liquid container 30 or incubated separately from the deviceand then added to liquid container 30, for example for performing abackup test (e.g., a backup strep test) using rapid testing techniques,e.g., rapid strep testing techniques. As used in the presentapplication, including in the claims, in the context of backup testing,“rapid” testing techniques (such as “rapid” strep testing techniques)refer to the type of test, rather than implying that the test isperformed and provides results soon after the sample is obtained fromthe patient; indeed, for performing backup testing, the rapid testingtechniques are typically performed well after the sample has beenobtained from the patients, such as a number of hours thereafter, andtypically include incubation of the sample.

Liquid 22 (e.g., saliva) may be spit directly by the patient into liquidcontainer 30 or transferred by a healthcare worker from anothercontainer into which the patient spit. Alternatively, in the case ofsaliva, the saliva may be collected from the patient's mouth by havingthe patient suck on a swab or other absorbent collecting element, suchas flocked swabs or cotton rolls.

For applications in which testing device 20 comprises plunger 40 andplunger housing 74, such as described above, liquid 22 is typicallyreceived in liquid container 30 before plunger 40 has been inserted intoplunger housing 74 (or liquid container 30).

As shown in FIG. 1B, pressure is applied to drive liquid 22 contained inliquid container 30 of testing device 20 through filter 32, such asusing one or more of the techniques for applying pressure describedhereinabove. For applications in which testing device 20 comprises theone or more valves 60, the pressure also drives liquid 22 through theone or more valves 60 after the liquid is driven through filter 32. Forapplications in which liquid container 30 is shaped so as to define theone or more openings 51, as described hereinabove, the pressure drivesliquid 22 through the one or more openings 51. Typically, toward the endof the application of the pressure, some air trapped in liquid container30 is blown through filter 32, helping to expel most of liquid 22remaining in filter chamber 36 and generally dry the filter chamber. Forapplications in which testing device 20 comprises waste liquidreceptacle 46, applying the pressure drives liquid 22 contained inliquid container 30 through filter 32, then through the one or morevalves 60, and then into waste liquid receptacle 46. For someapplications in which testing device 20 comprises filter chamber 36,applying the pressure also drives some of liquid 22 into filter chamber36. For some applications, testing device 20 further comprises a releasebutton that pushes on filter chamber 36 to extract any remaining gargledfluid upon completion of application of the pressure (configuration notshown).

As shown in FIG. 1C, for applications in which testing device 20comprises upstream component 70 and downstream component 72, upstreamcomponent 70 is decoupled from downstream component 72, in order toexpose and provide access to filter 32. Instead removing plunger 40 fromliquid container 30 might cause some of liquid 22 to spray out of liquidcontainer.

As shown in FIG. 1A-D, for some application in which testing device 20comprises filter chamber 36, the pressure is applied while filter 32 isremovably disposed upstream of filter chamber 36 with filter 32partially covering inlet 38. For some of these applications, afterapplying the pressure and before testing for the presence of theparticulate trapped by filter 32, at least a portion of filter 32 ispushed into filter chamber 36, such as shown in FIGS. 1D-F. For example,the at least a portion of filter 32 may be pushed into filter chamber 36using an elongate member 56, such as shown in FIG. 1D-E, using plungerhead 42 (configuration not shown), or using gas pressure and/or suction(configuration not shown). For applications in which filter chamber 36comprises one or more pressure-activated valves 50, such as describedhereinabove, the elongate member 56 (e.g., swab 58 thereof) drivesliquid 22 in filter chamber 36 out of filter chamber 36 through the oneor more pressure-activated valves 50, into waste liquid receptacle 46 ifprovided, such as shown in FIG. 1E.

As shown in FIGS. 1E-F, for some applications, a sample is taken fromfilter 32 (either from a surface of the filter or of the filter itself,such as a small part of the filter) using elongate member 56 (e.g., swab58 thereof), and the sample is tested, outside testing device 20, forthe presence of the particulate. This testing may, for example, be anovernight backup test, e.g., an overnight backup strep test. The backuptest may be performed by placing the sample (optionally while still onswab 58) into a test tube 85 containing growth medium 87 (e.g., ToddHewitt broth, tryptic soy broth, Columbia Broth, Nutrient Broth, orThioglycollate broth), capping the test tube, and incubating the testtube, as is known in the art. Optionally, growth medium 87 has theproperties of the high-concentration liquid growth medium described indetail hereinbelow.

Alternatively, for some applications, the entire filter 32 is removedfrom testing device 20 and tested, outside testing device 20, for thepresence of the particulate. If such testing is a rapid strep test, themethod may conclude with this test, and not continue with theperformance of a test in testing device 20, as described hereinbelowwith reference to FIGS. 1G-H. For example, the rapid strep test may useany of the testing techniques described hereinbelow with reference toFIG. 12 regarding external analysis device 1010, with or without firstculturing.

As shown in FIGS. 1G-H, the method further comprises testing, withintesting device 20, for the presence of particulate trapped by filter 32while filter 32 is disposed in testing device 20. For applications inwhich testing device 20 comprises the one or more valves 60, the testingis performed while the one or more valves 60 are closed. Alternativelyor additionally, for applications in which testing device 20 comprisesfilter chamber 36, the testing is performed within filter chamber 36while filter 32 is disposed at least partially in the filter chamber.

For some applications, the testing is performed by:

-   -   applying an extraction reagent 86 to filter 32, such as shown in        FIG. 1G; for applications in which testing device 20 comprises        filter chamber 36, the extraction reagent 86 is typically        applied to filter 32 while filter 32 is in filter chamber 36; as        mentioned above, for applications in which testing device 20        comprises the one or more valves 60, the testing is performed        while the one or more valves 60 are closed so that extraction        reagent 86 is retained by filter 32 rather than passing through        the filter, and    -   after applying extraction reagent 86, inserting a test strip 88        into testing device 20 (e.g., into filter chamber 36) and        examining the test strip to test for the presence of the        particulate, such as shown in FIG. 1H; optionally, filter 32 is        mixed after application of extraction reagent 86 but before        insertion of test strip 88.

Reference is still made to FIGS. 1A-H. In an application of the presentinvention, a system 90 (labeled in FIG. 1A) is provided that comprises:

-   -   a liquid 22 including at least one substance selected from the        group of substances consisting of gargled fluid, saliva not        swabbed from the throat of a patient, and an incubated culture        medium containing a biological sample; and    -   testing device 20, which comprises (a) liquid container 30        containing the liquid 22, (b) the one or more valves 60, (c)        filter 32, disposed in or downstream of liquid container 30 and        upstream of the one or more valves 60, and (d) liquid-pressure        source 34, which is arranged to apply pressure to drive liquid        22 contained in liquid container 30 through filter 32 and then        through the one or more valves 60.

Reference is now made to FIG. 2, which is a schematic illustration of atesting device 120 for testing for presence of particulate in liquid 22,in accordance with an application of the present invention. Other thanas described below, testing device 120 is similar to testing device 20,described hereinabove with reference to FIGS. 1A-H, and may implementany of the features thereof.

Testing device 120 comprises a filter 132 that is disposed at leastpartially, e.g., entirely, within a filter chamber 136. By contrast,filter 32 of testing device 20 is removably disposed upstream of filterchamber 36 with filter 32 partially covering inlet 38. Other than thisfeature, filter 132 may have any of the features of filter 32 describedhereinabove with reference to FIGS. 1A-H, including material propertiesand dimensions.

Filter chamber 136 may implement any of the features of filter chamber36, described hereinabove with reference to FIGS. 1A-H. Typically,filter chamber 136 comprises one or more pressure-activated valves 50(such as a plurality, as shown in FIG. 2), not disposed at an inlet 138.Inlet 138 may implement any of the features of inlet 38 describedhereinabove with reference to FIGS. 1A-H. In applications in which aplurality of pressure-activated valves 50 are provided, the bottom-mostvalve may serve to allow the flushing of the remaining liquid 22.

Testing device 120 may be used as described hereinabove with referenceto FIGS. 1A-H. The pressure described hereinabove with reference to FIG.1B is applied while filter 132 is disposed at least partially (e.g.,entirely) within filter chamber 136. The pressure drives liquid 22 fromliquid container 30 to filter chamber 136, then through filter 132, andthen through the one or more pressure-activated valves 50, andoptionally into waste liquid receptacle 46, if provided. Typically,liquid container 30 is not shaped so as to define the one or moreopenings 51 described hereinabove with reference to FIGS. 1A-H.

For some applications, filter 132 is disposed surrounding at least 270degrees, typically 360 degrees, of a central longitudinal axis 124 offilter chamber 136, such that all or substantially all of liquid 22 thatpasses out of filter chamber 136 must pass through filter 132. For someapplications, filter 132 covers all of the one or morepressure-activated valves 50. For some applications, filter 132 coversat least 80%, such as 100%, of the internal surface of filter chamber136. For some applications, such as shown in FIG. 2, filter 132 isshaped as a receptacle.

Reference is now made to FIGS. 3A-B, which are schematic illustrationsof a testing device 220 for testing for presence of particulate inliquid 22, in accordance with an application of the present invention.Other than as described below, testing device 220 is similar to testingdevice 20, described hereinabove with reference to FIGS. 1A-H, and mayimplement any of the features thereof.

Testing device 220 further comprises a frangible seal 226 that removablyblocks liquid flow into an inlet 238 of a filter chamber 236. Forexample, frangible seal 226 may comprise a pliable material (such assilicone) that is easily torn, such as shown in Option A in FIG. 3A, ora rigid material that is easily broken (e.g., shaped so as define slitsto aid in breaking), such as shown in Option B in FIG. 3A. Typically,filter 32 of testing device 220, like filter 32 of testing device 20, isremovably disposed upstream of filter chamber 236 with filter 32partially covering inlet 238 of filter chamber 236. When pressure isapplied, as described hereinabove with reference to FIG. 1B,substantially all of liquid 22 is driven out of liquid container 30,either the one or more openings 51 or valves 60 described herein.Thereafter, before testing for the presence of the particulate trappedby filter 32, frangible seal 226 is broken, such as using elongatemember 56 (e.g., swab 58 thereof), as shown in FIG. 3A, or using plungerhead 42 (configuration not shown), and at least a portion of (e.g., theentirely of) filter 32 is pushed into filter chamber 236. Because liquidcontainer 30 is substantially empty of liquid 22, only a minimal amountof liquid 22 enters filter chamber 236. Therefore, filter chamber 236typically does not comprise any pressure-activated valves 50 notdisposed at an inlet 238, because drainage of liquid is not required.

For some applications, filter chamber 236, before frangible seal 226 isbroken, contains a material, such as a rapid test solution (e.g., arapid strep test) in liquid or solid (e.g., powdered) form. This maysimplify the use of the testing device because the material is notflushed during the application of pressure, and thus does not need to beadded during use after applying the pressure.

For some applications, testing device 20 further comprises a support forfilter 32 (e.g., the configuration of frangible seal 226 shown in OptionB in FIG. 3A), disposed at least partially between inlet 38 and filter32. During application of pressure, as described hereinbelow withreference to FIG. 1B, the support helps prevent filter 32 from enteringfilter chamber 36, which might occur if inlet 38 is relative wide. Thesupport is easily breakable or flexible such that filter 32 can stillreadily be pushed into filter chamber 36. For example, the support maycomprise a very thin plastic sheet (like a plastic bag) that has holessuch that the support provides enough support for the filter to rest onand not puncture, and also very flexible so that it can easily be pushedinto filter chamber 36 together with filter 32. Alternatively, thesupport may comprise a harder or firmer material that is easilybreakable, e.g., may comprise slits to enable easy breaking. Optionally,plunger head 42 is configured to break the support (configuration notshown). The support may comprise an elastomer and/or be perforated withopenings, e.g., having an average diameter of between 0.2 and 5 mm.

Reference is now made to FIG. 3C, which is a schematic illustration of atesting device 290 for testing for presence of particulate in liquid 22,in accordance with an application of the present invention. Other thanas described below, testing device 290 is similar to testing device 20,described hereinabove with reference to FIGS. 1A-H, and may implementany of the features thereof. Liquid container 30 is not shaped so as todefine the one or more openings 51 or the one or more valves 60described hereinabove with reference to FIGS. 1A-H. Instead, in order toallow liquid 22 to pass through the peripheral portion of filter 32 notdisposed over inlet 38, the downstream surface of liquid container 30 isshaped so as define a plurality of elongate indentations 292 that extendradially inward to the edge of inlet 38. The liquid 22 that is driventhrough the peripheral portion of filter 32 enters the indentations anddrains from the indentations into filter chamber 36. This configurationallows for the entire filter upstream surface area to be utilized whileallowing the air trapped in liquid container 30 to blow out most ofremaining liquid 22 from filter chamber 36 to leave the filter chambergenerally dry.

Reference is now made to FIGS. 4A-C, which are schematic illustrationsof a testing device 320 for testing for presence of particulate inliquid 22, in accordance with an application of the present invention.Reference is also made to FIGS. 5A-B, which are schematic illustrationsof a testing device 420 and a testing device 520, respectively, fortesting for presence of particulate in liquid 22, in accordance withrespective applications of the present invention. Other than asdescribed below, testing devices 320, 420, and 520 are similar totesting device 20, described hereinabove with reference to FIGS. 1A-H,and may implement any of the features thereof.

For applications in which the one or more valves 60 are provided, suchas shown in FIGS. 4A-C and 5A-B, the one or more valves 60 are one ormore first valves 60, and testing devices 320, 420, and 520 furthercomprise one or more second pressure relief valves 361, which are influid communication with liquid container 30 and are disposed upstreamof filter 32. For some applications, the one or more first valves 60comprise one or more first pressure-activated valves 60 configured toopen upon exposure to a first pressure gradient across the one or morefirst pressure-activated valves 60, and the one or more second pressurerelief valves 361 are configured to open upon exposure to a secondpressure gradient across the one or more second pressure relief valves361, the second pressure gradient greater than the first pressuregradient. Alternatively, the one or more valves 60 are not provided; forexample, the wall of liquid container 30 may be shaped so as to definethe one or more openings 51 described hereinabove with reference toFIGS. 1A-H.

The one or more second pressure relief valves 361 allow drainage ofliquid 22 if excess pressure occurs in liquid container 30, such as iffilter 32 becomes clogged during the application of pressure describedhereinabove with reference to FIG. 1B.

Reference is made to FIGS. 4A-C. For some applications, liquid-pressuresource 34 comprises a plunger 340, which comprises (a) a plunger shaft341 and (b) a plunger head 342 disposed at a downstream end portion ofplunger shaft 341 and shaped so as to be insertable into liquidcontainer 30. Plunger 340 (including plunger head 342 and plunger shaft341) may implement any of the configures of plunger 40 describedhereinabove with reference to FIGS. 1A-H. Testing device 320 comprisesone or more unfiltered liquid receptacles 344 (e.g., vials). The one ormore second pressure relief valves 361 comprise one or more secondpressure relief valves 348 that are in fluid communication with the oneor more unfiltered liquid receptacles 344. For some applications, theone or more unfiltered liquid receptacles 344 are disposed along plungershaft 341, such as shown. Optionally, the one or more unfiltered liquidreceptacles 344 are removably coupled to plunger 340. Typically, the oneor more unfiltered liquid receptacles 344 are shaped so as to definevents to allow the escape of air as liquid 22 enters. Optionally, theone or more unfiltered liquid receptacles 344 contain an antibacterialagent, such as described hereinbelow with reference to FIG. 9 regardingwaste liquid receptacle 46.

Reference is made to FIG. 5A. For some applications, testing device 420further comprises waste liquid receptacle 46, which is coupled to liquidcontainer 30 downstream of filter 32 (and of the one or more valves 60,if provided). Liquid-pressure source 34 is arranged to apply pressure todrive liquid 22 contained in liquid container 30 through filter 32, thenthrough the one or more openings 51 or the one or more valves 60, ifprovided, and then into waste liquid receptacle 46. The one or moresecond pressure relief valves 361 comprise one or more second pressurerelief valves 448 that are in fluid communication with waste liquidreceptacle 46 not via filter 32.

Reference is made to FIG. 5B. For some applications, the one or moresecond pressure relief valves 361 comprise one or more second pressurerelief valves 548 that are in fluid communication with outside testingdevice 520.

Reference is made to FIGS. 6A-C, which are schematic illustrations of atesting device 620 for testing for presence of particulate in liquid 22,in accordance with an application of the present invention. Other thanas described below, testing device 620 is similar to testing device 320,described hereinabove with reference to FIGS. 4A-C and may implement anyof the features thereof. In addition, other than as described below,testing device 620 is similar to testing device 20, describedhereinabove with reference to FIGS. 1A-H, and may implement any of thefeatures thereof.

Testing device 620 comprises one or more unfiltered liquid receptacles644 (e.g., vials). The one or more second pressure relief valves 361,348 are in fluid communication with the one or more unfiltered liquidreceptacles 644, such that when pressure is applied, as describedhereinabove with reference to FIG. 1B, a portion of the unfilteredliquid 22 is driven into the one or more unfiltered liquid receptacles644. After applying the pressure, a sample of liquid 22 in the one ormore unfiltered liquid receptacles 644 is taken, and the sample istested, outside testing device 20, for the presence of the particulate,using any overnight or rapid test (e.g., rapid strep test) including ornot including incubation. This may simplify the process of taking asample for backup test, e.g., a backup strep test (and may even get abetter sample of bacteria). Optionally, the one or more unfilteredliquid receptacles 644 contain culture media, e.g., including red bloodcells.

Reference is now made to FIGS. 7A-C and 8A-E, which are schematicillustrations of a testing device 720 for testing for presence ofparticulate in liquid 22, in accordance with an application of thepresent invention. Other than as described below, testing device 720 issimilar to the testing devices described hereinabove with reference toFIGS. 1A-6C, and may implement any of the features thereof; testingdevice is particularly similar to testing device 220, describedhereinabove with reference to FIGS. 3A-B. Unless otherwise described,reference numerals in FIGS. 7A-C and 8A-E refer to like parts asreference numerals in FIGS. 1A-H based on the last two digits.

Testing device 720 comprises a liquid-pressure source 734, whichcomprises a plunger 740, which comprises a plunger head 742 that isshaped so as to be insertable into a liquid container 730. Plunger 740is shaped so as to define a waste liquid receptacle 746.

Plunger 740 is also shaped so as to define a filter chamber 736. Filterchamber 736 typically does not comprise any pressure-activated valves50. Testing device 720 further comprises a frangible seal 726 thatremovably blocks liquid flow into an inlet 738 of filter chamber 736.Frangible seal 726 may implement any of the features of frangible seal226 described hereinabove with reference to FIGS. 3A-B.

For some applications, testing device 720 comprises a cap 792, which isremovably coupled to a distal end of liquid container 730 (i.e., to theend opposite the end into which plunger 740 is inserted). A proximalwall 794 of cap 792 defines a distal wall of liquid container 730. Forsome applications, cap 792 is shaped so as to define an unfilteredliquid receptacle 744, and proximal wall 794 of cap 792 comprises one ormore second pressure relief valves 761 that (a) are in fluidcommunication with unfiltered liquid receptacle 744 and, when cap 792 iscoupled to liquid container 730, with liquid container 730, and (b) aredisposed upstream of filter 732.

Before use (e.g., during manufacture), cap 792 is removably coupled toliquid container 730, such as by twisting the cap onto liquid container730, as shown in FIG. 8A. Also before use, plunger 740 is not coupled toliquid container 730. Optionally, plunger 740 has a distal protectivecover 796, which is removed before use.

Liquid 22 (such as gargled fluid, saliva not swabbed from the throat ofa patient, or an incubated culture medium containing a biologicalsample) is received in liquid container 730.

As shown in FIG. 8B, plunger 740 is inserted into liquid container 730after removing cap 792.

As shown in FIG. 8C, plunger 740 is pushed until the distal end of theplunger reaches proximal wall 794 of cap 792. This pushing appliespressure to liquid 22, such as described hereinabove with reference toFIG. 1B.

As shown in FIG. 8D, cap 792 is removed from liquid container 730, suchas by twisting the cap, and, optionally, further pushing the plungeruntil the plunger pushes off the cap, in order to expose a filter 732.The cap is disposed.

As shown in FIG. 8E, at least a portion (e.g., the entirely) of filter732 is pushed into filter chamber 736, such as using elongate member 56,which also breaks frangible seal 726. (The filter may tear, as shown,leaving a portion of the filter outside filter chamber 736, e.g.,connected at a periphery of the filter to liquid container 730, asshown.)

The use of testing device 720 may continue as described hereinabove withreference to FIGS. 1E-H, mutatis mutandis.

Reference is now made to FIG. 9, which is a schematic illustration of atesting device 820 for testing for presence of particulate in liquid 22,in accordance with an application of the present invention. Other thanas described below, testing device 820 is similar to the testing devicesdescribed hereinabove with reference to FIGS. 1A-8E, and may implementany of the features thereof. Similarly, any of testing devices describedherein may implement the features of FIG. 9, mutatis mutandis.

Testing device 820 comprises waste liquid receptacle 46, which containsan antibacterial agent 824, such as a detergent, thiomersal, bleach, oriodine (I/KI) to kill any bacteria that passes through filter 32, toreduce the risk of contamination upon accidental exposure to the liquidin waste liquid receptacle 46.

For some applications, an inlet 838 of a filter chamber 336 of testingdevice 820 has an inlet area that is less than a greatestcross-sectional area of filter chamber 336, the inlet area and thegreatest cross-sectional area measured in respective planes parallel toeach other. For example, the inlet area may be no more than 95%, such asno more than 90%, e.g., no more than 80% of the greatest cross-sectionalarea of filter chamber 336. Providing this narrowing of filter chamber336 at inlet 838 may help retain filter 32 in filter chamber 336 duringwithdrawal of elongate member 56, as described hereinabove withreference to FIG. 1F. Testing devices 320, 420, 520, 620, 1020, and1120, described herein with reference to FIGS. 4A-C, 5A, 5B, 6A-C, 14B,and 15B, respectively, are also shown comprising filter chamber 336;these testing devices may alternatively comprise filter chambers 36,136, 236, or 736, mutatis mutandis.

Reference is now made to FIGS. 10A-C, which are schematic illustrationsof a testing device 920 for testing for presence of particulate inliquid 22, in accordance with an application of the present invention.(Filter 32 is shown in partial cut-away view to show the one or morenon-pressure-activated valves 960 described below.) Other than asdescribed below, testing device 920 is similar to the testing devicesdescribed hereinabove with reference to FIGS. 1A-9, and may implementany of the features thereof.

The one or more valves 60 of testing device 920 comprise one or morenon-pressure-activated valves 960. For example, the one or morenon-pressure-activated valves 960 may be opened and closed by aligningand non-aligning, respectively, sets of openings in two discs 962A and962B of the one or more non-pressure-activated valves 960, eithermanually or automatically by the testing device, such as describedhereinbelow. Other manual and automated configurations will be readilyapparent to those skilled in the art who have read the presentapplication.

During use, liquid 22 is received in a liquid container 930, as shown inFIG. 10A, typically while the one or more non-pressure-activated valves960 are in an opened state (e.g., with the openings in disc 962A alignedwith the openings in disc 962B), thereby allowing liquid 22 to passthrough the one or more valves and the filter, optionally into a wasteliquid receptacle 946 if provided, as shown in FIGS. 10A-B. Typically,while the one or more non-pressure-activated valves 960 are open,pressure is applied using a liquid-pressure source such as thosedescribed herein.

Thereafter, as partially shown in FIG. 10C, the one or morenon-pressure-activated valves 960 are closed (e.g., by rotating at leastone of discs 962A and 962B so that their respective openings are notaligned with one another) and filter 32 is tested for the presence ofparticulate trapped by filter 32, such as described hereinabove withreference to FIGS. 1G-H, mutatis mutandis. The closed one or more valvesretain extraction reagent 86 in filter 32 by preventing the extractionagent from passing through the filter.

As described hereinabove, for some applications, the testing devicesdescribed herein comprise a liquid-pressure source that is arranged toapply pressure to drive liquid contained in the liquid container throughthe filter and, optionally, then into the waste liquid receptacle. Forsome of these applications, the testing device is configured toautomatically (typically, non-electrically) close one or morenon-pressure-activated valves of the testing device after the plungerapplies the pressure to drive the liquid contained in the liquidcontainer through the filter and then through the one or morenon-pressure-activated valves. For some of these applications, thetesting device is configured such that motion of the plungerautomatically (typically, non-electrically) closes the one or morenon-pressure-activated valves after the plunger applies the pressure todrive the liquid contained in the liquid container through the filterand then through the one or more non-pressure-activated valves. Althoughthe testing device is described in this and the following configurationsas non-electrically closing the one or more non-pressure-activatedvalves, the testing device may alternatively electrically close the oneor more non-pressure-activated valves, such as using a motor.

Reference is now made to FIGS. 10D-K, which are schematic illustrationsof a testing device 1420 for testing for presence of particulate inliquid 22, in accordance with an application of the present invention.Other than as described below, testing device 1420 is similar to thetesting devices described hereinabove with reference to FIGS. 1A-9 and10A-C, and may implement any of the features thereof, mutatis mutandis.Testing device 1420 comprises a liquid-pressure source 1434, whichcomprises a plunger 1440, which comprises a plunger head 1442 that isshaped so as to be insertable into a liquid container 1430. Testingdevice 1420 typically further comprises a waste liquid receptacle 1446,which is coupled to liquid container 1430 downstream of filter 32.Plunger 1440 is arranged to apply pressure to drive liquid 22 containedin liquid container 1430 through filter 32 and then through one or morenon-pressure-activated valves 1460 of testing device 1420, and intowaste liquid receptacle 1446, if provided, as shown in FIGS. 10I-J.

As shown in FIG. 10K, testing device 1420 is configured such thatrotational motion of plunger 1440 automatically (typically,non-electrically) closes the one or more non-pressure-activated valves1460 of testing device 1420 after plunger 1440 applies the pressure todrive liquid 22 contained in liquid container 1430 through filter 32 andthen through the one or more non-pressure-activated valves 1460. Forexample, the last turn of plunger 1440, or a fraction of the last turn(which may or may not include the last portion of the last turn), mayautomatically close the one or more non-pressure-activated valves 1460.

For some applications, plunger 1440 is shaped so as to define one ormore plunger threads 1466, and an internal wall of liquid container 1430is shaped so as to define one or more liquid-container threads 1468 thatengage the one or more plunger threads 1466 such that rotation ofplunger 1440 advances plunger 1440 in a downstream direction withinliquid container 1430. Advancing plunger 1440 helps control the speed ofthe advancement and helps maintain steady advancement against pressurein liquid container 1430.

For some applications, the one or more non-pressure-activated valves1460 comprise two discs 1462A and 1462B, which are shaped so as todefine respective sets of openings 1463A and 1463B, for example asdescribed hereinabove with reference to FIGS. 10A-C. For theseapplications, testing device 1420 is configured such that rotationalmotion of plunger 1440 automatically closes the one or morenon-pressure-activated valves 1460 by rotating at least one of the twodiscs 1462A and 1462B with respect to the other of the discs, afterplunger 1440 applies the pressure to drive liquid 22 contained in liquidcontainer 1430 through filter 32 and then through the one or morenon-pressure-activated valves 1460. For example, the last turn ofplunger 1440, or a fraction of the last turn (which may or may notinclude the last portion of the last turn), may automatically rotate theat least one of the discs. For example, ridges 1465A on plunger head1442 may engage, via filter 32, corresponding ridges 1465B on anupstream surface of disc 1462A after plunger 1440 has been advanced in adownstream direction into contact with disc 1462A. Alternatively oradditionally, for some applications, testing device 1420 comprises oneor more tabs 1467 that rotate the upper disc and/or break the capsulesdescribed hereinbelow.

For some applications, testing device 1420 comprises one or more reagentcontainers 1471, such as capsules, that contain one or more extractionreagents 86 (either the same type of extraction reagents or differingextraction reagents). Reagent containers 1471 are disposed at leastpartially in liquid container 1430, such that upon opening of thecontainers, such as by crushing, tearing, or breaking, extractionreagents 86 are released into liquid container 1430, typically nearfilter 32. For example, testing device 1420 may configured such thatrotational motion of plunger 1440 automatically opens reagentscontainers 1471, such as by bringing one or more respective protrusions1473 into contact with the reagent containers. For example, a fractionof the last turn (or the last turn), may automatically open reagentscontainers 1471. Typically, a fraction of last turn (may or may notinclude the last portion of the last turn) opens reagents containers1471, and the fraction occurs after the fraction of the last turn thatcloses the one or more non-pressure-activated valves 1460, such that theone or more valves are closed before the reagents are released.

Reference is made to FIGS. 10D-G, which illustrate a portion of a methodfor using testing device 1420 for testing liquid 22 for the presence ofthe particulate. This method is optional, and testing device 1420 is notnecessarily used in this manner and thus does not necessarily comprisethe elements necessary for use in this manner. These techniques may bealso be practiced in combination with any of the testing devicesdescribed herein for which they are applicable, mutatis mutandis.

In this portion of the method, the user typically receives testingdevice 1420 with the elements thereof removably coupled together, asshown in FIG. 10D. The user removes plunger 1440 of liquid-pressuresource 1434 and a container 1490 from the body of testing device 1420,as shown in FIG. 10E; for example, plunger 1440 may be removed fromliquid container 1430 and container 1490 may be removed from a cavitydefined by plunger 1440. Liquid 22 is received from the patient intocontainer 1490 (step not shown). Liquid 22 is poured from container 1490into liquid container 1430, as shown in FIG. 10E. Plunger 1440 isreinserted into liquid container 1430, as shown in FIG. 10G.

Reference is now made to FIGS. 10L-M, which are schematic illustrationsof a testing device 1520 for testing for presence of particulate inliquid 22, in accordance with an application of the present invention.Other than as described below, testing device 1520 is similar to testingdevice 1420 described hereinabove with reference to FIGS. 10D-K. and mayimplement any of the features thereof, mutatis mutandis. Testing device1520 comprises a spring 1521, which is biased to hold slightly separateddiscs 1562A and 1562B of one or more non-pressure-activated valves 1560of testing device 1520, thereby creating a fluid flow path through theopenings of the discs, as shown in FIG. 10L. The downstream advancing ofthe plunger pushes the upper disc 1562A downstream and thus the discstogether (and compresses the spring), as shown in FIG. 10M, therebyblocking fluid flow through the openings. The discs typically do notrotate with respect to one another in this configuration.

Reference is now made to FIGS. 10N-O, which are schematic illustrationsof a testing device 1620 for testing for presence of particulate inliquid 22, in accordance with an application of the present invention.Other than as described below, testing device 1620 is similar to testingdevices 1420 and 1520 described hereinabove with reference to FIGS.10D-K and FIGS. 10L-M, respectively, and may implement any of thefeatures thereof, mutatis mutandis. Testing device 1620 comprises one ormore flaps 1621, which, in an initial configuration, do not blockopenings 1663A and 1663B defined by discs 1662A and 1662B, respectively,of one or more non-pressure-activated valves 1660 of testing device1620, as shown in FIG. 10N. Typically, flaps 1621 are somewhat springyand biased to hold slightly separated discs 1562A and 1562B of one ormore non-pressure-activated valves 1560 of testing device 1520. As shownin FIG. 10O, when plunger 1470 is advanced in a downstream directioninto contact with disc 1662A, which in turn pushes upstream disc 1662Acloser to downstream disc 1662B, thereby causing the one or more flaps1621 to block openings 1663A and 1663B (such as by displacing ordeforming the flaps). The discs typically do not rotate with respect toone another in this configuration.

Reference is now made to FIGS. 10P-Q, which are schematic illustrationsof a testing device 1720 for testing for presence of particulate inliquid 22, in accordance with an application of the present invention.Other than as described below, testing device 1720 is similar to testingdevices 1420, 1520, and 1620 described hereinabove with reference toFIGS. 10D-K, FIGS. 10L-M, and FIGS. 10N-0, respectively, and mayimplement any of the features thereof, mutatis mutandis. Testing device1720 comprises one or more compressible spacers 1733, which holdslightly separated discs 1762A and 1762B of one or morenon-pressure-activated valves 1760 of testing device 1720, therebycreating a fluid flow path through the openings of the discs, as shownin FIG. 10P, by holding the discs at a sufficient distance from eachother such that one or more plugs 1729 (e.g., spherical plugs) do notplug openings 1763A of upper disc 1762A. The downstream advancing of theplunger pushes upper disc 1762A downstream and thus the discs together(and compresses the compressible spacers 1733), as shown in FIG. 10Q,thereby causing the one or more plugs 1729 to block openings 1763A. Oneor more springs 1731 may be provided to push the one ore more plugs 1729against openings 1763A. Alternatively, a spring similar to spring 1521of testing device 1520 may be provided instead of or in addition tocompressible spacers 1733. The discs typically do not rotate withrespect to one another in this configuration.

Reference is now made to FIGS. 11A-E, which are schematic illustrationsof testing device 20 further comprising one or more heating elements1000, in accordance with respective applications of the presentinvention. Although these configurations are illustrated with respect totesting device 20, they may also be combined with the other testingdevices described herein, mutatis mutandis. These configurations enableincubation of liquid 22 within testing device 20.

In these configurations, testing device 20 further comprises one or moreheating elements 1000 that are configured to heat filter 32 and/orliquid 22 in liquid container 30 at a generally constant temperature,typically in the range of 20 and 50 degrees C., such as in the range of30 to 40 degrees C. It is noted that the temperature is considered“generally constant” even if the temperature varies somewhat, such asbecause of cycling on and off of the one or more heating elements 1000.

Heating elements 1000 may comprise, for example, electrical heatingelements or chemical heating elements (e.g., a heating bag). Forapplications in which heating elements 1000 are electrical, they arecoupled in electrical communication with a power supply 1002, such as anexternal power supply (e.g., the power grid) or an external or internalbattery. For example, the coupling may be done using a conventionalelectrical plug or USB interface. For some applications, testing devicecomprises control circuitry 1004 and a heat sensor 1006 (e.g., athermocouple or other thermostat), and control circuitry 1004 isconfigured to drive heating elements 1000 responsively to a temperaturesensed using heat sensor 1006 in order to maintain the generallyconstant temperature mentioned above.

For some applications, heating elements 1000 are disposed external tomain body of testing device 20, such as supported by a stand 1001, suchas shown in FIG. 11A.

For other applications, such as shown in FIG. 11B, in whichliquid-pressure source 34 comprises plunger 40 that comprises plungerhead 42 that is shaped so as to be insertable into liquid container 30,such as described hereinabove, the one or more heating elements 1000 aredisposed in the plunger 40, such as in plunger head 42, e.g., separatedfrom the distal end of the plunger head by a layer of material such thatliquid 22 does not interfere with the electrical current.

For still other applications, such as shown in FIG. 11C, the one or moreheating elements 1000 are disposed downstream of filter 32 (as shown) orupstream of filter 32 (configuration not shown).

For other applications, such as shown in FIGS. 11D-E, the one or moreheating elements 1000 are disposed around liquid container 30.

For some applications, the one or more heating elements 1000 areconfigured to heat filter 32 and/or liquid 22 in liquid container 30after most or nearly all (e.g., at least 90%) of liquid 22 has beendriven out of liquid container 30 and the particulate has been trappedby filter 32, such as shown in FIGS. 11B and 11C (the configurationshown in FIG. 11D can alternatively be used with the plunger pushedfarther down than illustrated, and the configuration shown in FIG. 11Acan also be used). Typically, growth medium 87 (e.g., Todd Hewitt brothor tryptic soy broth) is placed in testing device 20 (e.g., in liquidcontainer 30, filter 32, or the distal downstream surface of plungerhead 42) before the heating is performed, in order to incubate theparticulate in liquid 22 and/or filter 32. For example, such heating mayallow a rapid test (e.g., a rapid strep test) to be performed afterincubation of the particulate trapped by the filter 32, for example forbetween 1 and 24 hours, in order to achieve more accurate results.Optionally, growth medium 87 has the properties of thehigh-concentration liquid growth medium described in detail hereinbelow.

For other applications, the one or more heating elements 1000 areconfigured to heat filter 32 and/or liquid 22 in liquid container 30while most (e.g., at least 90%) or all of liquid 22 remains in liquidcontainer 30 before being driven out of liquid container 30 and throughfilter 32, e.g., by pushing with plunger head 42, such as shown in FIGS.11D and 11E (the configurations shown in FIGS. 11B and 11C can also beused with plunger pushed down less than illustrated, and theconfiguration shown in FIG. 11A can also be used). Typically, growthmedium 87 (e.g., Todd Hewitt broth or tryptic soy broth) is placed intesting device 20 (e.g., in liquid container 30, filter 32, or thedistal downstream surface of plunger head 42) before the heating isperformed, in order to incubate the particulate in liquid 22.Thereafter, after waiting, for example for between 1 and 24 hours,liquid 22 is driven through filter 32, and the filter is tested forparticulate, for example using a rapid test (e.g., a rapid strep test)performed within or outside of testing device 20. Such incubation mayachieve more accurate results. Optionally, growth medium 87 has theproperties of the high-concentration liquid growth medium described indetail hereinbelow.

Depending on the characteristics of the particular type of filter 32used, the filter may be damaged (e.g., degraded) by immersion in heatedliquid 22 for 1 to 24 hours. Therefore, in order to prevent suchpossible damage, testing device 20 may be oriented with filter 32 aboveliquid 22 and liquid-pressure source 34 (e.g., plunger 40) below filter32, such that liquid 22 is not in contact with filter 32 during theheating, such as shown in FIG. 11E. Other configurations may also beused, such the configuration shown in FIG. 11A or FIG. 11B, mutatismutandis.

Alternatively, in order to prevent the above-mentioned possible damage,for some applications, such as shown in FIG. 11D, liquid container 30comprises a frangible dividing waterproof or water-resistant membrane1008 upstream of filter 32 (e.g., spaced at least 1 mm, such as at least3 mm, at least 5 mm, or at least 10 mm, from the filter), which isolatesfilter 32 from liquid 22 in liquid container 30. For some applications,membrane 1008 is elastic, which among other things, may allow insertionof plunger head 42 into liquid container 30. After completion ofincubation, pushing plunger 40 causes the plunger to break (e.g., tear)membrane 1008 and allow liquid 22 to come in contact with filter 32 forpassage therethrough. Other configurations may also be used, such theconfiguration shown in FIG. 11A, mutatis mutandis.

Reference is now made to FIG. 12, which is a schematic illustration of amethod for performing a test, e.g., a backup strep test, in accordancewith an application of the present invention. A sample is taken fromfilter 32 (either from a surface of the filter or of the filter itself,such as a small part of the filter), e.g., using elongate member 56(e.g., swab 58 thereof), such as described hereinabove with reference toFIGS. 1E-F. The sample is analyzed using an external analysis device1010, such as a nucleic acid amplification RST technique, such asisothermal amplification, e.g., using Alere™ i (Abbott Laboratories,Waltham, Mass., USA), or real-time quantitative polymerase chainreaction (qPCR) assaying, typically without first incubating the sample.Alternatively, the sample is incubated (either before placing the samplein external analysis device 1010 or inside device 1010 by device 1010)and external analysis device 1010 tests the sample using a techniquesuch as lateral flow immunoassaying, an ELISA-based RST, anantibody-coated-beads-based RST, a nucleic-acid-based RST, or afluorescent immunoassaying (FIA).

Reference is now made to FIGS. 13A-C, which are schematic illustrationsof methods for performing a backup test, e.g., a backup strep test, inaccordance with respective applications of the present invention.Although these configurations are illustrated with respect to testingdevice 20, they may also be combined with the other testing devicesdescribed herein, mutatis mutandis. Prior to liquid 22 being passedthrough filter 32, some of liquid 22, e.g., gargled fluid or saliva notswabbed from the patient's throat, is removed as a sample for a backuptest. FIG. 13A shows an absorbent element, e.g., a swab 58, e.g., aflocked swab, a cotton swab, or a polyester swab, being inserted intoliquid 22 and then placed into test tube 85 containing growth medium 87.For some applications, liquid 22, or a portion of liquid 22, istransferred into the container, e.g., test tube 85, by other means, suchas for example, pouring, using a syringe, using a pipette, or a pump.Growth medium 87 may be a liquid growth medium, a dehydrated growthmedium, or a gel growth medium. Optionally, growth medium 87 has theproperties of the high-concentration liquid growth medium described indetail hereinbelow. Typically, test tube 85 does not contain agar.

Reference is now made to FIG. 13D, which is a flowchart depicting amethod for performing a backup strep test using rapid strep test (RST)techniques on gargled fluid after incubation, in accordance with someapplications of the present invention. Examples of the method of FIG.13D are provided in the experimental data set forth hereinbelow in thesection entitled, “Measuring Group A Beta-Hemolytic StreptococcusBacteria in Throat Gargle: Results of Overnight Growth in Liquid Media,Assayed by Rapid Strep Test.” In step 1200 the gargled fluid isincubated for at least 12 hours and/or less than 75 hours in acontainer, e.g., test tube 85, that contains a liquid growth medium, adehydrated growth medium, or a gel growth medium. As illustrated by theexperimental data, the total volume of gargled fluid and growth mediumis typically at least 0.45 ml and/or less than 3.6 ml. In someapplications, the gargled fluid is mixed with the growth medium beforeincubation. Typically, the container containing the growth medium doesnot contain agar.

In step 1202, after incubation, an RST, e.g., a lateral flow test, isperformed on the mixture of gargled fluid and growth medium. For someapplications, the RST may be one of the following: an ELISA-based RST,an antibody-coated-beads-based RST, a nucleic-acid-based RST, and afluorescent immunoassaying (FIA) RST. As supported by the experimentaldata set forth hereinbelow in the section entitled, “Measuring Group ABeta-Hemolytic Streptococcus Bacteria in Throat Gargle: Results ofOvernight Growth in Liquid Media, Assayed by Rapid Strep Test,”, anumber of methods used for performing the RST yield usable results, asfollows:

-   -   RST is performed on the mixture of gargled fluid and growth        medium while the gargled fluid and growth medium are in the        container. This method of RST is referred to as “whole tube RST”        in the experimental data.    -   At least a portion, e.g., at least 0.05 ml, e.g., 0.1 ml, of the        mixture of gargled fluid and growth medium is transferred to        another container, and the RST is performed on the portion of        the gargled fluid and growth medium in the other container. This        method of RST is referred to as “sample RST” in the experimental        data. For some applications, the portion of the mixture is        transferred by inserting an absorbent element, e.g., a swab,        e.g., a flocked, cotton, or polyester swab, into the mixture of        gargled fluid and growth medium and then placing the swab into        the other container. Alternatively, if an absorbent element,        e.g., a swab, was used to transfer liquid 22, e.g., the gargled        fluid, into the container with growth medium, then that same        absorbent element, e.g., swab may be removed and used to        transfer the portion of the mixture into the other container for        “sample RST.” For some applications, the portion of the mixture        is transferred into the container, e.g., test tube 85, by other        means, such as for example, pouring, using a syringe, using a        pipette, or a pump.    -   At least a portion of the mixture of gargled fluid and growth        medium, after incubation, is filtered, e.g., passed through a        filtration membrane (optionally, using any of the filtering        devices described herein), and the RST is performed on the        filter. This method of RST is referred to as “filter RST” in the        experimental data.

Results of a clinical trial performed by the inventors, includingtwenty-eight patients, are shown in Tables 1A-1D of FIGS. 19A-D,respectively, of the experimental data set forth hereinbelow in thesection entitled, “Measuring Group A Beta-Hemolytic StreptococcusBacteria in Throat Gargle: Results of Overnight Growth in Liquid Media,Assayed by Rapid Strep Test.” Gargled fluid was collected from each ofthe 28 patients and tested using “whole tube RST” and/or “filter RST”after incubation for at least 21 hours and/or less than 25 hours(further details regarding parameters of the tested systems are setforth in the experimental data). As shown in Tables 1A-1D, 19 systemsyielded true positive RST results, which corresponded to 19 of thepatients who were clinically positive for GAS pharyngitis (truepositive), and nine systems yielded true negative results, whichcorresponded to nine patients who were clinically negative for GASpharyngitis (true negative). See Table 2 of FIG. 20 in the experimentaldata for parameters from 78 additional experimental systems that yieldedtrue positive RST results. These additional experimental systems eachcontained either (a) gargled fluid which was spiked with Group AStreptococcal (“GAS”) bacteria, or (b) a GAS bacteria suspension in apure buffer.

Reference is now made to FIG. 13E, which is a flowchart depicting amethod for performing a backup strep test using rapid strep test (RST)techniques on saliva not swabbed from a patient's throat afterincubation, in accordance with some applications of the presentinvention. Examples of this method are provided in the experimental dataset forth hereinbelow in the section entitled, “Measuring Group ABeta-Hemolytic Streptococcus Bacteria in Saliva Sample: Results ofOvernight Growth in Liquid Media, Assayed by Rapid Strep Test.” In step1204 the saliva swab is incubated for at least 12 hours and/or less than75 hours in a container, e.g., test tube 85, that contains a liquidgrowth medium, a dehydrated growth medium, or a gel growth medium. Insome applications, the saliva is mixed with the growth medium beforeincubation. Typically, the container containing the growth medium doesnot contain agar. For some applications, the patient sucks on the swab,or the swab is rubbed on the patient's tongue and/or cheek. In thismanner, the saliva is received on the swab, e.g., a flocked swab, acotton swab, or a polyester swab, from the patient's mouth, and the swabis then placed directly into the container that contains the growthmedium. Alternatively, the patient spits saliva into the container.

In step 1206, after incubation, an RST, e.g., a lateral flow test, isperformed on the mixture of saliva and growth medium. For someapplications, the RST may be one of the following: an ELISA-based RST,an antibody-coated-beads-based RST, a nucleic-acid-based RST, and afluorescent immunoassaying (FIA) RST. As supported by the experimentaldata set forth hereinbelow in the section entitled, “Measuring Group ABeta-Hemolytic Streptococcus Bacteria in Saliva Sample: Results ofOvernight Growth in Liquid Media, Assayed by Rapid Strep Test,” andsimilarly to as described hereinabove with reference to FIG. 13D, anumber of methods were used for performing the RST, as follows:

-   -   “Whole tube RST,” as described hereinabove, mutatis mutandis.    -   “Sample RST,” as described hereinabove, mutatis mutandis.    -   “Filter RST,” as described hereinabove, mutatis mutandis.    -   After incubation, at least a portion of the mixture of saliva        and growth medium is transferred to another container by        removing the swab from the container containing the growth        medium and placing the swab into the other container, and the        RST is performed on the swab in the other container. This method        of RST is referred to as “swab RST” in the experimental data.

In a clinical trial performed by the inventors, 28 patients were askedto suck on a flocked swab for about ten seconds. The saliva swabs werethen inoculated onto blood plates, and beta-hemolytic colonies werecounted using a light table. As illustrated by Table 5 of FIG. 23 in theexperimental data set forth hereinbelow in the section entitled,“Measuring Group A Beta-Hemolytic Streptococcus Bacteria in SalivaSample: Results of Overnight Growth in Liquid Media, Assayed by RapidStrep Test,” 18 out of 19 (94.7%) saliva swabs from subjects who wereclinically positive for GAS pharyngitis were found to contain a numberof colony-forming units (CFUs) of GAS ranging from four to “too numerousto count.” A false negative was obtained for 1 of the 19 saliva swabs.

As illustrated by the experimental data, experiments were also carriedout by the inventors using saliva swab simulations by dipping swabs intopure GAS bacteria suspensions (referred to as “saliva swab simulation 1”in the experimental data) or into gargled fluid that was spiked with GASbacteria (referred to as “saliva swab simulation 2” in the experimentaldata). The data presented in Table 7 of FIG. 25 represent an experimentusing “saliva swab simulation 1” which compared the total absorbanceplus elution of GAS bacteria onto a plate from three different swabmaterials: cotton, polyester, and flocked. The flocked swabs appear tohave the highest absorption plus elution efficiency, however the cottonand polyester swabs provide useful results as well. The data presentedin Table 8 of FIG. 26 represent an experiment using “saliva swabsimulation 2” showing that flocked swabs may be used as an efficient wayof transferring liquid, e.g., saliva, or gargled fluid, into the culturemedium.

Almost all saliva swab clinical samples which were inoculated into ToddHewitt (TH) broth and assayed by backup methods using RST methodsyielded either true positive or true negative results for all subjectsenrolled in phase 2 of the Proof of Concept Clinical Trial, seen inTable 9 of FIG. 27. The data presented in Table 9 describe ClinicalTrial saliva swabs that were incubated in TH culture broth and were thenassayed using backup test methods performed using RST methods. TheFilter RST method had a sensitivity of 90% and the Swab RST method had asensitivity of 80%.

Reference is now made to FIGS. 14A-C, which are schematic illustrationsof a testing device 1020 for testing for presence of particulate inliquid 22, in accordance with an application of the present invention.Although testing device 1020 is illustrated as being similar to testingdevice 20 described hereinabove with reference to FIGS. 1A-H, thetechniques of testing device 1020 may also be combined with the othertesting devices described herein, mutatis mutandis.

Testing device 1020 comprises:

-   -   liquid container 30 for containing liquid 22;    -   filter 32, disposed in or downstream of liquid container 30; and    -   plunger head 42, which (a) is shaped so as to be insertable into        liquid container 30, (b) is configured to apply pressure to        drive liquid 22 from liquid container 30 through filter 32,        and (c) has downstream surface 80.

Downstream surface 80 is at least partially coated with a solid (e.g.,dehydrated and/or powdered) or semi-solid (e.g., gel and/or paste)growth medium 1022. For example, growth medium 1022 may comprise agar.

For some applications, a cap 1024 is provided that is configured to becoupled to and fully cover growth medium 1022 on downstream surface 80of plunger head 42. For example, cap 1024 may be transparent to enableobservation of the culture on downstream surface 80 without removing thecap.

Typically, plunger head 42 is shaped so as to be insertable into liquidcontainer 30 so as to form a movable seal with a wall of liquidcontainer 30. For some applications, testing device 1020 furthercomprises a plunger shaft 1031, and plunger head 42 is disposed at adownstream end portion of plunger shaft 1031. Plunger 40 (includingplunger head 42 and plunger shaft 1031) may implement any of theconfigures of plunger 40 described hereinabove with reference to FIGS.1A-H. For some applications, an area of downstream surface 80 of plungerhead 42 is between 0.3 and 100 cm2, such as between 0.3 and 30 cm2. Forsome applications, testing device 1020 further comprises waste liquidreceptacle 46, coupled to liquid container 30 downstream of filter 32.

For some applications, a method for using testing device 1020 comprises:

-   -   pushing plunger head 42 to apply pressure to drive liquid 22        from liquid container 30 through filter 32;    -   touching downstream surface 80 of plunger head 42 to filter 32;        particulate 1023, such as bacteria, on filter 32 are captured by        growth medium 1022 on downstream surface 80; and    -   assessing downstream surface 80 of plunger head 42 for        biological growth.

Typically, downstream surface 80 is placed directly in an incubatorbefore assessing, thereby obviating the need to use another device totake a backup sample and plate it onto agar. Downstream surface 80 isoptionally accessed by decoupling upstream component 70 from downstreamcomponent 72, such as described hereinabove with reference to FIGS.1B-C.

For some applications, liquid 22 includes at least one substanceselected from the group of substances consisting of gargled fluid,saliva not swabbed from the throat of a patient, and an incubatedculture medium containing a biological sample.

For some applications, downstream surface 80 of plunger head 42 isassessed for biological growth of a biological particulate selected fromthe group consisting of: a microorganism, a fungus, a bacterium, aspore, a virus, a mite, a biological cell, a biological antigen, aprotein, a protein antigen, and a carbohydrate antigen. For someapplications, plunger head 42 is heated before downstream surface 80 ofplunger head 42 is assessed for biological growth.

Reference is now made to FIGS. 15A-C, which are schematic illustrationsof a method for using a testing device 1120 for testing for presence ofparticulate in liquid 22, in accordance with an application of thepresent invention. Although testing device 1120 is illustrated as beingsimilar to testing device 20 described hereinabove with reference toFIGS. 1A-H, the method described with reference to testing device 1120may also be combined with the other testing devices described herein,mutatis mutandis.

The method comprises:

-   -   pushing plunger head 42 to apply pressure to drive liquid 22        from liquid container 30 of testing device 1120 through filter        32;    -   touching downstream surface 80 of plunger head 42 to filter 32;    -   thereafter, touching downstream surface 80 of plunger head 42 to        culture medium 1126 contained in a culture-medium container        1128, such as a petri dish; for example, culture medium 1126 may        include agar;    -   heating culture-medium container 1128; and    -   assessing culture-medium container 1128 for biological growth.

For some applications, liquid 22 includes at least one substanceselected from the group of substances consisting of gargled fluid,saliva not swabbed from the throat of a patient, and an incubatedculture medium containing a biological sample.

For some applications, culture-medium container 1128 is assessed forbiological growth of a biological particulate 1023 selected from thegroup consisting of: a microorganism, a fungus, a bacterium, a spore, avirus, a mite, a biological cell, a biological antigen, a protein, aprotein antigen, and a carbohydrate antigen.

Downstream surface 80 is optionally accessed by decoupling upstreamcomponent 70 from downstream component 72, such as described hereinabovewith reference to FIGS. 1B-C.

For some applications, plunger head 42 is rotated while touchingdownstream surface 80 of plunger head 42 to filter 32 to increase thesample taken from filter 32, such as by macerating or grinding thefilter. For applications in which downstream surface 80 is decoupledfrom upstream component 70 by rotation, this rotation may itselfincrease the sample taken from filter 32.

For some applications, downstream surface 80 of plunger head 42 isrough, i.e., is shaped so as to define many small protrusions 1122, suchas like sandpaper, or with plastic protrusions, in order to collect abetter sample of particulate 1023 by macerating or grinding the filter.

For some applications, touching downstream surface 80 of plunger head 42to filter 32 comprises grinding filter 32 with rough downstream surface80.

For some applications, the method further comprising testing, withintesting device 1120, for the presence of biological particulate 1023trapped by filter 32, such as described hereinabove. In theseapplications, the sample taken from downstream surface 80 of plungerhead 42 is used to perform a backup test, e.g., a backup strep test, forthe rapid test performed inside testing device 1120, as describedhereinabove.

Reference is now made to FIGS. 16A-B, which are schematic illustrationsof a testing system 1300, in accordance with an application of thepresent invention. Testing system 1300 comprises a testing machine 1310and a testing device 1320 for testing for the presence of particulate ina liquid 22 (shown in FIGS. 18B-F). Testing device 1320 is configured tobe removably inserted into testing machine 1310 for performing a test.Testing device 1320 may be disposable, while testing machine 1310 istypically reused many times with separate testing devices 1320. Testingdevice may optionally implement any of the features of the other testingdevices described herein, mutatis mutandis.

Reference is also made to FIG. 17, which is a schematic exploded view oftesting device 1320, in accordance with an application of the presentinvention. Testing device 1320 comprises:

-   -   a liquid container 1330 for containing liquid 22, liquid        container 1330 shaped so as to define an upstream opening 1376        and a downstream opening 1378;    -   a filter 32, removably disposed in liquid container 1330; and    -   a plunger head 1342 that (a) is shaped so as to be insertable        into liquid container 1330 so as to form a movable seal with a        wall of liquid container 1330, and (b) is arranged such that        when pushed, plunger head 1342 applies pressure to drive liquid        22 contained in liquid container 1330 through filter 32 and then        through downstream opening 1378.

Testing device 1320 is configured such that rotation of plunger head1342 radially compresses filter 32 toward a central longitudinal axis1364 of plunger head 1342, as shown in FIG. 18F, described hereinbelow.This concentrates filter 32 in a more compact volume to better enablethe performance of a test for the particulate, as described hereinbelowwith reference to FIG. 18F. For some applications, testing device 1320is configured such that the rotation of plunger head 1342 crushes filter32, which may improve the sensitivity of the subsequent testing.

For some applications, plunger head 1342 comprises a protrusion 1366(best seen in FIG. 17), and testing device 1320 is configured such thatthe rotation of plunger head 1342 causes protrusion 1366 to moveradially toward central longitudinal axis 1364 of plunger head 1342. Forexample, protrusion 1366 may be coupled to a base 1368 that can slideradially within a track 1369, such as shown in the bottom view in FIG.17, or protrusion 1366 may be directly slidable within a track.

For some applications, liquid container 1330 is shaped so as to define afilter-support surface 1371 surrounding downstream opening 1378.Filter-support surface 1371 supports a radial portion 1373 of filter 32excluding a central portion 1375 of filter 32 (the central portion 1375is typically removably disposed over downstream opening 1378).Filter-support surface 1371 is shaped so as to define a spiral groove1377. Protrusion 1366 is configured to engage spiral groove 1377 throughfilter 32. Testing device 1320 is configured such that the rotation ofplunger head 1342 (such as by between one-third of a turn to 10 turns)causes spiral groove 1377 to guide protrusion 1366 radially towardcentral longitudinal axis 1364 of plunger head 1342.

Reference is now made to FIGS. 18A-F, which are schematic illustrationsof a method for using testing system 1300 to test for the presence ofthe particulate in liquid 22, in accordance with an application of thepresent invention.

As shown in FIGS. 18A-B, plunger head 1342 of testing device 1320 iscoupled to a plunger shaft 1341 of testing machine 1310. The othercomponents of testing device 1320, including but not limited to liquidcontainer 1330, are removably inserted into testing machine 1310,typically after liquid 22 is contained in liquid container 1330.

As shown in FIG. 18C, plunger shaft 1341 pushes plunger head 1342applies pressure to drive liquid 22 contained in liquid container 1330through filter 32 and then through downstream opening 1378.

As shown in FIGS. 18D-E, plunger shaft 1341 rotates plunger head 1342 toradially compress filter 32 toward central longitudinal axis 1364, shownin FIG. 18F. Optionally, liquid container 1330 includes a narroweroutlet portion, and radially compresses the filter also deposits all ora portion of the filter in the narrower outlet portion.

As shown in FIG. 18F, filter 32 is tested for particulate trapped infilter 32, including, for example, applying extraction reagent 86, asdescribed hereinabove.

For some applications, testing machine 1310 comprises a waste liquidreceptacle 1346, into which liquid 22 is driven after passing throughfilter 32. Typically, waste liquid receptacle 1346 is large enough toaccommodate tests performed using several testing devices 1320.

Reference is again made to FIG. 17. In an application of the presentinvention, a testing kit 1390 is provided for use with liquid 22.Testing kit 1390 comprises:

-   -   liquid container 1330 for containing liquid 22, liquid container        1330 shaped so as to define an upstream opening 1376 and a        downstream opening 1378;    -   filter 32, disposed in or downstream of liquid container 1330;        and    -   plunger head 1342 that (a) is shaped so as to be insertable into        liquid container 1330 so as to form a movable seal with a wall        of liquid container 1330, and (b) is arranged such that when        pushed, plunger head 1342 applies pressure to drive liquid 22        contained in liquid container 1330 through filter 32 and then        through downstream opening 1378.

Testing kit 1390 does not comprise a plunger shaft. Instead, plungerhead 1342 is removably coupled to plunger shaft 1341 of testing machine1310, as described above with reference to FIGS. 18A-B.

Although testing kit 1390 has been described with reference to liquidcontainer 1330 and plunger head 1342, testing kit 1390 may alternativelycomprise any of the other liquid containers described herein or anotherliquid container known in the art, and/or plunger head 1342 mayalternatively comprise any of the other plunger heads described hereinor another plunger head known in the art.

For some applications, sterile packaging is provided, in which at leastliquid container 1330, plunger head 1342, and filter 32 are removablydisposed. The sterile packaging comprises one or more sterile packages;for example, each element may be removably disposed in a separate one ofthe packages, and/or more than one the elements may be disposed in asingle one of the packages.

Although techniques for testing, including rapid testing, are generallydescribed herein as being performed for detecting strep, they may alsobe used to detect other biological particulate, such as a virus. Forexample, for detecting a virus, the filters described herein may captureepithelial cells that include the virus.

Measuring Group a Beta-Hemolytic Streptococcus Bacteria in ThroatGargle: Results of Overnight Growth in Liquid Media, Assayed by RapidStrep Test

In some applications of the present invention, group A streptococcusbacteria (GAS) can be detected in throat gargle by two primary methodtypes: Direct (“Immediate”) methods and Indirect (“Backup”) methods.Immediate methods yield results faster than Backup methods (<20 minutesvs. 12-48 hours) but are not as sensitive (higher rate of falsenegatives).

In a clinical experiment performed by the inventors, Backup methods forGAS detection in throat gargle were tested. The experimental data isbased on two types of GAS throat gargle simulations: pure GAS liquidsuspension and throat gargle spiked with GAS. The Clinical Trial data isbased on throat gargles obtained from patients with GAS pharyngitis whowere enrolled in phase 2 of a Proof of Concept Clinical Trial (ProtocolNumber: STRP.P001, SNIH Clinical Trial Number: NCT03231098, Shaare ZedekMedical Center Helsinki IRB Number: SZMC-0181-17).

Materials and Methods

Bacterial Culture: 10 GAS strains were used: 1 standard control strainand 9 wildtype strains. The control GAS strain was American Type CultureCollection (“ATCC”) 19615, a strain often used for quality control, andthe wildtype GAS strains were isolated during Clinical Trials andlabeled WT-1 through WT-9. All GAS bacteria used in experiments weretaken from 1-7 days old cultures on blood agar plates stored at 4-8° C.

Growth conditions: The bacteria were routinely grown in a 37° C.incubator, without agitation. Liquid cultures were grown in 4 mL plastictest tubes, with liquid volumes of 0.45 mL, 0.6 mL, 1.0 mL, 1.1 mL, and3.6 mL after inoculation. Cultures were incubated for 12-75 hours.

Growth media: Blood plate media: Standard 90 mm plate (Petri dishes)containing TSA+5% sheep blood. Blood plates were purchased from Hylabs(Rehovot, Israel, Cat. No. PD-049). Liquid media: Tryptic Soy Broth(“TSB”), which is a well-known general-purpose growth media. Sterile TSBtubes were purchased from Hylabs (Cat. No. TT139). Liquid media: ToddHewitt broth (“TH”), which is a media specifically developed to growStreptococci. TH powder was purchased from Sigma Aldrich (Missouri, USA,Cat. No. T1438-500g). The media was prepared and sterilized byfiltration through 0.2 um filtration units. The liquid growth media wasprepared with 4.5 times the concentration recommended in theinstructions. At this higher concentration, the liquid growth media hadthe following concentrations: glucose: 9 g/L; nitrogen source: 135 g/L;inorganic molecules: 22.05 g/L; and total solids: 166.5 g/L (as shown inthe 4.5 row of Table 11, described hereinbelow.

Bacterial suspensions: Pure GAS bacterial suspensions were made bytransferring GAS colonies from culture into sterile Phosphate BufferSaline (“PBS”).

Bacterial counts: 0.05 mL or 0.1 mL samples of bacterial suspensions orthroat gargles were inoculated onto blood plates without dilution andwith using the appropriate limiting dilutions (dilutions of 10-fold to8000-fold) and beta-hemolytic colonies were counted using a light table.

Throat gargle: Throat gargles were obtained by gargling 10-11 mL PBS forapproximately 10 seconds.

Gargle spiked with GAS: Pure GAS liquid suspensions were added to gargleand diluted with gargle as necessary.

RST methods: Lateral flow immuno-assay RST kits were purchased fromMoore Medical (Connecticut, USA, Cat. No. 82792). Standard RST:Conducted according to manufacturers' instructions. Swab containingspecimen sample was placed into a tube containing 8 drops of RSTsolutions, agitated slightly, and removed after 1-3 minutes. RSTdipstick was then added to tube and removed after 5 minutes. 0.1 mLSample RST: Similar to standard RST. 0.1 mL of specimen sample was addedto tube containing RST solutions instead of a swab. Whole tube RST: 8drops of RST solutions were added directly into tubes containing liquidculture media (0.4 mL, 0.9 mL, or 3.0 mL) incubated with gargle orsimulated gargle, and RST dipstick was added to tube 1-3 minutes afteraddition of RST solutions. Filter RST: Culture media incubated withgargle or simulated gargle was filtered, membrane filter containingconcentrated specimen sample was placed into a tube, 8 drops of RSTsolutions were added, and tube contents were mixed by a blunt tip for30-45 seconds. The RST dipstick was added to the filter mixtureapproximately 3 minutes after addition of RST solutions.

Summary of Results

Of the 28 patients enrolled in phase 2 of the Proof of Concept ClinicalTrial, 19 patients had true positive results from Backup Test methodsperformed using RST methods and 9 patient had true negative results fromBackup Test methods performed using RST methods, as displayed in Table1A-1D of FIGS. 19A-D, respectively. The data in Table 1A of FIG. 19Apresents the gargle Backup Test methods performed using RST results for28 patient throat gargles. Each patient throat gargle was tested usingone or two systems (total systems=53). Each system consisted of 0.2 mLinoculated gargle plus either 0.4 mL or 0.9 mL of TH culture media, fora total volume of either 0.6 mL or 1.1 mL. The calculated GAS withineach inoculated gargle added to a system ranged from 36 CFU to 80,400CFU. Systems were incubated for 21-25 hours at 37° C. and then processedusing either the Filter RST method or Whole Tube RST method.

The data in Table 1B-1D of FIGS. 19B-D, respectively, present thesensitivity and specificity of the gargle Backup Test methods performedusing RST results in general and separated by method. The data indicatesthat the Filter RST method has higher sensitivity (100%) than the WholeTube RST method (95%).

Overall, 78 experimental systems containing simulated GAS garglesyielded true positive RST results, as detailed in Table 2 of FIG. 20.The data in Table 2 describes 78 systems which resulted in a positivelateral flow RST immunoassay after incubating a sample of simulatedgargle containing GAS in culture media under a variety of conditions.Conditions include: incubating culture at 37° C. for 12 to 75 hours;using 2 different growth media; inoculation volumes of 0.05 mL, 0.1 mL,0.2 mL, and 0.6 mL; overall volumes (inoculate+culture media) of 0.45mL, 0.6 mL, 1.0 mL, 1.1 mL, and 3.6 mL; total number of starting GASbacteria ranging between 18 to 567,000; and using 10 different GASstrains. All Backup method simulation tests using GAS bacteriasuspension in a pure buffer, including tests which are not included inTable 2, consisted of at least 95% true positives. Backup method garglesimulation tests using gargle fluid spiked with GAS, including testswhich are not included in Table 2, yielded a majority of true positiveresults, but were not as sensitive as pure GAS suspension due toinherent variability of the simulation and/or flaws in the model ofspiking gargled fluid with GAS.

Minimum incubation time was 12 hours, as set forth in Table 3 of FIG.21. The data in Table 3 describes an experiment where 9 systems weretested by lateral flow RST immunoassay after incubating a 0.2 mL sampleof simulated gargle, either pure GAS suspension or gargle spiked withGAS, into 0.9 mL of Todd Hewitt culture media. Systems tested at 4 and 8hours yielded negative RST, while systems tested at 12 hours yieldedpositive RST.

The data in Table 4 of FIG. 22 describe different lateral flow RSTimmunoassay methods and strength of RST results after incubating 0.2 mLof either a sample of simulated gargle containing GAS (four data points)or a sample of actual GAS pharyngitis patient gargle in 0.9 mL ToddHewitt culture media (eight data points). The data suggest that of thethree methods tested, the Filter RST method yields superior results andis the most sensitive method for detecting GAS using RST afterincubation in culture media. The first eight rows of data from Table 4(patient data) are also included in Table 1 (which also includesexperimental collected performed after Table 4 was produced), while thelast for rows of data (stimulations) are not included in Table 1 becausethe additional data in Table 1 rendered this data no longer relevant tosupport the conclusion because of the additional clinical data.

Conclusions

These experimental data support the Backup method for GAS detection inthroat gargle that involves the incubation of a sample of unfilteredthroat gargle in liquid culture media for 12 to 75 hours followed bylateral flow RST immunoassay. A total of 53 systems from 28 patientsenrolled in phase 2 of the Proof of Concept Clinical Trial all yieldedeither true positive or true negative results. A total of 78experimental systems yielded positive Backup Test methods performedusing RST results in multiple conditions. The Filter RST Backup methodis presented as the most sensitive Backup Test method performed using aRST method, but all Backup Test methods performed using RST methods weresatisfactory.

Measuring Group a Beta-Hemolytic Streptococcus Bacteria in SalivaSample: Results of Overnight Growth in Liquid Media, Assayed by RapidStrep Test

In some applications of the present invention, group A streptococcusbacteria (GAS) can be detected from saliva swab by Indirect (“Backup”)methods. In a clinical experiment performed by the inventors, Backupmethods for GAS detection from saliva swab were tested. The experimentaldata is based on GAS growth simulations and the Clinical Trial data isbased on saliva swabs obtained from patients with GAS pharyngitis whowere enrolled in phase 2 of a Proof of Concept Clinical Trial (ProtocolNumber: STRP.P001, SNIH Clinical Trial Number: NCT03231098, Shaare ZedekMedical Center Helsinki IRB Number: SZMC-0181-17).

Materials and Methods

Bacterial Culture: 10 GAS strains were used: 1 standard control strainand 9 wildtype strains. The control GAS strain was American Type CultureCollection (“ATCC”) 19615, a strain often used for quality control, andthe wildtype GAS strains were isolated during Clinical Trials andlabeled WT-1 through WT-9. All GAS bacteria used in experiments weretaken from 1-7 days old cultures on blood agar plates stored at 4-8° C.

Growth conditions: The bacteria were routinely grown in a 37° C.incubator, without agitation. Liquid cultures were grown in 4 mL plastictest tubes, with liquid volumes of 0.9-1.1 mL after inoculation.Cultures were incubated for 12-75 hours.

Growth media: Blood plate media: Standard 90 mm plate (Petri dishes)containing TSA+5% sheep blood. Blood plates were purchased from Hylabs(Rehovot, Israel, Cat. No. PD-049). Liquid media: Todd Hewitt broth(“TH”), which is a media specifically developed to grow Streptococci. THpowder was purchased from Sigma Aldrich (Missouri, USA, Cat. No.T1438-500g). The media was prepared and sterilized by filtration through0.2 um filtration units. The liquid growth media was prepared with 4.5times the concentration recommended in the instructions. At this higherconcentration, the liquid growth media had the following concentrations:glucose: 9 g/L; nitrogen source: 135 g/L; inorganic molecules: 22.05g/L; and total solids: 166.5 g/L (as shown in the 4.5 row of Table 11,described hereinbelow.

Swabs: Flocked Swabs: Swabs with a tip of short nylon brush-like fibersdesigned for efficient absorption and elution, purchased from PuritanDiagnostics (Maine, USA, Cat. No. 25-3306-H). Cotton Swabs: Swabs with atip comprised of a cotton matrix, purchased from Kodan Medicam (BetShemesh, Israel, Cat. No. 1102245).

Polyester Swabs: Swabs with a tip comprised of a polyester matrix,manufactured by Puritan Diagnostics (Guilford, Main, USA), Cat. No.25-806 1PD SOLID).

Bacterial suspensions: Pure GAS bacterial suspensions were made bytransferring GAS colonies from culture into sterile Phosphate BufferSaline (“PBS”).

Gargle spiked with GAS: Throat gargles were obtained by gargling 10-11mL PBS for approximately 10 seconds and pure GAS suspensions were addedto gargle and diluted with gargle as necessary.

Saliva swabs: Saliva swabs were obtained from patients enrolled in theClinical Trial. Patients were asked to suck on a flocked swab forapproximately 10 seconds. Saliva swabs obtained from Clinical Trialsubjects were inoculated onto blood plates and beta-hemolytic colonieswere counted using a light table. Some saliva swabs were then inoculatedinto TH culture media and swab was left in culture media duringincubation. Both the culture media and the swab were later assayed byBackup methods performed using RST methods.

RST methods: Lateral flow immuno-assay RST kits were purchased fromMoore Medical (Connecticut, USA, Cat. No. 82792). Swab sample RST: Afterincubation, saliva swab was removed from culture media and placed into atube containing 8 drops of RST solutions, agitated slightly, and removedafter 1-3 minutes. RST dipstick was then added to tube and removed after5 minutes. 0.1 mL sample RST: Similar to swab RST. 0.1 mL of specimensample was added to tube containing RST solutions instead of a swab.Whole tube RST: In some cases, the 8 drops of RST solutions were addeddirectly into tubes containing GAS in liquid culture media (0.9-1.1 mL)and RST dipstick was added to liquid culture media tube 1-3 minutesafter addition of RST solutions. Filter RST: Culture media incubatedwith saliva swab was filtered, membrane filter was placed into a tube, 8drops of RST solutions were added, and tube contents were mixed by ablunt tip for 30-45 seconds. The RST dipstick was added to the filtermixture approximately 3 minutes after addition of RST solutions.

Saliva swab simulation 1: Swabs were dipped into tubes containing pureGAS bacteria suspensions and agitated up and down 12-20 times beforebeing removed for testing. Swabs were then inoculated onto blood platesand beta-hemolytic colonies were counted using a light table.

Saliva swab simulation 2: Swabs were dipped 5 times into tubescontaining gargle spiked with GAS bacteria and then dipped 5 times intoTH culture media to inoculate. Swabs were discarded prior to incubationof the culture media.

Bacterial counts: 0.05 mL or 0.1 mL samples of bacterial suspensionswere inoculated onto blood plates using the appropriate limitingdilutions (dilutions of 8,000-fold or 30,000-fold) and beta-hemolyticcolonies were counted using a light table.

Summary of Results

GAS was successfully captured from almost all plated saliva swab samplesof positive subjects enrolled in phase 2 of the Proof of ConceptClinical Trial, as seen in Table 5 of FIG. 23. The data in Table 5describe the range of GAS CFU amounts observed on the blood platesinoculated with Clinical Trial phase 2 subject saliva swabs. Most platedsaliva swabs from positive subjects successfully captured GAS with arange of 4 CFUs to TNTC, with only one case of false negative (pt. ID#033.VEN), yielding a capture rate of 94.7% (18/19). 84.2% of cases hadgreater than 20 CFUs, 73.7% of cases had greater than 40 CFUs, and 63.2%of cases had greater than 100 CFUs.

As presented in Table 6 of FIG. 24 (see also the next paragraph), fourof the saliva swab samples (Patients 12-15) from the Clinical Trial,after being inoculated onto the blood plates, were also tested usingBackup methods performed using RST methods, two of which yielded truepositive results. The Filter RST method yielded the strongest RST result(RST 4), and the Whole Tube RST method yielded the weakest RST result(RST 0). The Swab RST method was sensitive enough to yield a positiveresult even for a patient with a very low amount of GAS in the salivaswab sample (4 CFUs).

After performing the experiment reflected in Table 6, the inventorsappreciated that the data presented in Table 6 is invalid due toinaccurate testing. Due to the removal of some of the sample (forinoculating onto blood plates) prior to testing, as described above, theBackup methods using RST methods yielded inaccurate results, because thefull sample was not tested. Subsequent clinical trial samples weretested properly utilizing the complete saliva sample (Patients 17-34),as described hereinbelow with reference to Table 8 of FIG. 26.

Saliva swab simulation 1 shows that flocked swabs are the preferred swabfor obtaining a salvia swab sample, as can be seen in Table 7 of FIG.25. The data in Table 7 present an experiment which compared the totalabsorbance plus elution of GAS onto a plate from three different swabmaterials: cotton, polyester, and flocked. Swabs were dipped into 0.6 mLof pure GAS liquid suspension and then inoculated onto a blood plate.The flocked swab showed 3 to 5 times more total absorbance plus elutionefficiency using three different GAS concentrations.

Saliva swab simulation 2 shows that flocked swabs, when used toinoculate a sample into TH culture broth for a Backup Test performedusing RST methods, are as efficient as direct liquid transfer, as can beseen in Table 8 of FIG. 26. The data in Table 8 present an experimentwhich compared methods for transferring gargle spiked with GAS intoculture media (“inoculation methods”). Using a flocked swab forinoculation yielded a positive Backup Test performed using RST methodscomparable to using a pipette to transfer 0.2 mL (RST 3).

Almost all saliva swab clinical samples which were inoculated into ToddHewitt (TH) broth and assayed by Backup methods using RST methodsyielded either true positive or true negative results for all subjectsenrolled in phase 2 of the Proof of Concept Clinical Trial, seen inTable 9 of FIG. 27. The data presented in Table 9 describe ClinicalTrial saliva swabs that were incubated in TH culture broth and were thenassayed using Backup Test methods performed using RST methods. TheFilter RST method had a sensitivity of 90% and the Swab RST method had asensitivity of 80%.

Conclusions

These experimental data support the Backup method for GAS detectionusing a saliva sample via the incubation of a saliva swab in liquidculture media followed by lateral flow RST immunoassay. Plated clinicalsaliva swab samples displayed a 94.7% successful capture rate of GASwhich confirms that saliva samples are a viable alternative to garglingin cases where gargling is not possible. Saliva swab simulations supportthe concept that Backup Test methods performed using RST methods ofsaliva swabs incubated in liquid media is an efficient method for GASdetection. Additional saliva swab simulation data shows that flockedswabs increase the uptake and release of specimen samples compared toother swabs.

Clinical data from 18 samples demonstrates that a saliva swab BackupTest performed using RST methods in liquid media has high sensitivity(90%) and specificity (100%). Furthermore, the Filter Backup Testmethods performed using RST methods yielded a higher sensitivity (90%)than the Swab Backup method performed using RST methods (80%).

A liquid growth medium and a method of using the liquid growth mediumare provided for testing for the presence of group A streptococcusbacteria (GAS) in a sample of oral fluid obtained from a patient, inaccordance with respective applications of the present invention. Theliquid growth medium and/or the method may be used in combination withany of the techniques described hereinabove in which growth medium isused for testing for the presence of biological particulate, such asstrep, e.g., GAS. Although the liquid growth medium and the method aregenerally described hereinbelow as being appropriate for testing for thepresence of GAS, they may also be used to test for other types ofstreptococcus bacteria, other types of bacteria, a microorganism, afungus, a spore, a virus, a mite, a biological cell, a biologicalantigen, a protein, a protein antigen, or a carbohydrate antigen.

The liquid growth medium has a substantially greater total nitrogensource concentration and a substantially greater total solidsconcentration than conventional liquid growth media used for incubatingGAS. The liquid growth medium has a substantially greater osmotic value(indicative of the total concentration of molecules in the media) thanconventional liquid growth media. In particular, the liquid growthmedium typically has (a) a total nitrogen source concentration between75 and 300 g/L and (b) a total solids concentration between 92.5 and 370g/L.

The high-concentration liquid growth medium may be particularly usefulfor successfully growing low concentrations (typically between 100 and500 CFU/ml) of GAS present in samples of oral fluid, such as gargledfluid gargled by the patient or saliva not swabbed from a throat of thepatient. These samples of oral fluid typically contain many dozens oftypes (often over 100) of other types of interfering bacteria. Asdescribed below, the inventors have found that the use of conventional,lower concentration liquid growth media for testing for the presence ofGAS in samples of oral fluid (rather than samples swabbed from thetonsils, as is conventional in strep testing) results in consumption ofmost of the nutrients in the liquid growth medium by the interferingbacteria, leaving insufficient nutrients to grow the GAS of interest toan extent adequate for accurate testing.

Many bacterial liquid growth media are used commercially to grow Group Astreptococcus bacteria.

They all contain at least 2 of the following three types of components:

a. A sugar, usually glucose, as an energy source.

b. Nitrogen sources as building blocks for nitrogen and carbon.

c. Inorganic salts and molecules that serve as nutrients, as buffers tomaintain pH during growth and to maintain osmotic balance.

The table below shows the respective concentrations of theabovementioned three components in some of the widely used, commerciallyavailable liquid growth media formulations (which can be obtained frommany manufactures all over the world). The following are examples oftypical formulations.

TABLE 10 Nitrogen Inorganic Total Formulation name Glucose Sourcemolecules solids Todd Hewitt Broth 2 g/L 30 g/L 4.9 g/L 37 g/L BrainHeart Infusion 2 g/L 27.5 g/L 7.5 g/L 37 g/L Tryptic Soy Broth 2.5 g/L20 g/L 7.5 g/L 30 g/L Columbia Broth 2.5 g/L 23.1 g/L 9.41 g/L 35 g/LNutrient Broth None 20 g/L 5 g/L 25 g/L Thioglycollate broth 5.5 g/L20.5 g/L 3 g/L 29.75 g/L

Thus, a typical conventional liquid growth media for streptococcalgrowth will contain=<30 g/L of nitrogen sources, >10 g/L of Inorganicmolecules, >40 g/L of total solids. These conventional liquid growthmedia, having the respective concentrations as shown in Table 10, allenable good growth of GAS in pure form.

Furthermore, the use of a high-concentration liquid growth medium isconventionally believed to depress the growth of GAS. See, for example,Bernheimer, A. W. and Pappenheimer A. M. Jr., “Factors necessary formassive growth of Group A hemolytic Streptococcus”. Journal ofBacteriology, Volume 43(4), pages 481-494 (1941).

As described hereinabove, the liquid growth medium of the presentapplication has a substantially greater osmotic value (indicative of thetotal concentration of molecules in the media) than conventional liquidgrowth media. For some applications, the total nitrogen sourceconcentration is between 105 and 180 g/L, such as between 120 and 160g/L, and/or the total solids concentration is between 130 and 222 g/L,such as between 148 and 193 g/L.

Typically, the liquid growth medium has a pH of between 6 and 8.3, suchas between 7.0 and 8.0.

For some applications, the liquid growth medium has a total sugarconcentration of between 6 and 20, such as between 6 and 12. For some ofthese applications, the liquid growth medium has a glucose concentrationof between 7 and 10, such as between 8 and 9.5.

For some applications, an assembly is provided that includes the liquidgrowth medium and a sealed sterile container that contains the liquidgrowth medium.

For some applications, an assembly is provided that includes the liquidgrowth medium and a container that contains the liquid growth medium anda sample of oral fluid obtained from a patient, such as described above.

For some applications, a kit is provided that includes the liquid growthmedium and a lateral flow strep test strip, one or more extractionreagents, and/or a filter.

In an application of the present invention, a method of preparing theliquid growth medium includes adding a quantity of powdered growthmedium to a volume of distilled water, and stirring until the powderedgrowth medium is dissolved in the distilled water to produce the liquidgrowth medium. The quantity of powdered growth medium and the volume ofthe distilled water are typically selected such that the liquid growthmedium has (a) a total nitrogen source concentration between 75 and 300g/L and (b) a total solids concentration between 92.5 and 370 g/L. Theliquid growth medium may optionally have any of characteristicsdescribed above.

In an application of the present invention, a method is provided fortesting for the presence of GAS in a sample of oral fluid obtained froma patient, the method including:

-   -   generating a biological product by incubating the sample of oral        fluid for between 12 and 50 hours in a container that contains a        liquid growth medium, the liquid growth medium having (a) a        total nitrogen source concentration between 75 and 300 g/L        and (b) a total solids concentration between 92.5 and 370 g/L;        and    -   thereafter, performing a strep test using a rapid strep test        (RST) technique on the biological product.

For some applications, incubating includes incubating for between 16 and50 hours.

Typically, the container does not contain agar. Alternatively, thecontainer does contain some agar, but it is typically a relatively smallamount compared to conventional strep culturing techniques.

For some applications, performing the strep test using the RST techniqueincludes performing a lateral flow test. For some applications,performing the strep test includes applying one or more extractionreagents to the biological product.

Alternatively, for some applications, performing the strep test usingthe RST technique includes performing an RST technique selected from thegroup consisting of: an ELISA-based RST, an antibody-coated-beads-basedRST, a nucleic-acid-based RST, and a fluorescent immunoassaying (FIA)RST.

Typically, but not necessarily, the sample of oral fluid is selectedfrom the group consisting of: gargled fluid gargled by the patient, andsaliva not swabbed from a throat of the patient (e.g., spit by thepatient, or sucked onto a swab by the patient).

Alternatively, the sample of oral fluid is saliva swabbed from a tonsilof the patient.

For some applications, generating the biological product furtherincludes filtering the sample of oral fluid and the liquid growth mediumafter incubating. For some of these applications, performing the streptest using the RST technique includes performing the strep test usingthe RST technique on the filter. For some of these filteringapplications, the sample of oral fluid is saliva swabbed from a tonsilof the patient.

Typically, RST values below 0.25 (average of 5 and 10 minutes readings)are considered to be negative results. An RST value of 0.5 is indicativeof a bacteria concentration of at least 10,000 CFU/ml

The inventors performed experimentation where the lateral flow values ofpure systems grown in TH-1 and TH-10 were compared with the lateral flowvalues of TH-1 systems with added salt (NaCl) or sugar (Glucose) atincreasing concentrations. The Lateral flow value of TH-10 was similarto the values of TH-1+5% NaCl and 30% glucose.

5% Nacl and 30% glucose have similar Osmolarities, and inhibited theStrep to the same extent.

From this a value of about 180 MOsmomolar was calculated, and ademonstration of Osmolarity dependent Strep A growth inhibition wasshown, in agreement with scientific literature.

A. The following is an experimental setup as performed by the inventors:

1. Each system consisted of a 5 ml test tube, containing 1.1 ml growthmedia.

2. 0.1 ml bacterial suspensions were added to each system and growth wasstarted by incubation at 35.5° C., in air. Termination was done bywithdrawal from the incubator and immediate processing, or by storage at6-8° C. for up to 2 hours before processing.

3. The 0.1 ml bacterial suspensions were of 3 types:

-   -   (a) In “pure” systems the bacteria were suspended in sterile        Phosphate-Buffered Saline (“PBS”).    -   (b) In “Gargle” systems the bacteria were suspended in a gargle        solution. Gargle was obtained by gargling 10-11 ml of sterile        PBS for about 10 seconds and then transferring the gargle to a        collection cup.    -   (c) In “saliva” systems the bacteria were suspended in saliva.        Saliva was obtained by spitting into a collection cup.

4. Incubation was for a period of at least 4 hours but up to 3 days,depending on the experiment.

5. Two strains of GAS were used: the well-known “ATCC 19615” strain,which is used as a control strain in many diagnostic applications, and awild-type strain “WT-9,” which was isolated from a patient in a clinicaltrial performed on behalf of the inventors.

6. Bacterial stock suspensions were obtained by resuspending in PBS a1-4-days-old bacterial colony, grown at 35.5° C. on a blood agar platefor 1-2 days and then stored at 6-8° C. till used. The stock was diluted10-250,000 fold, depending on the experiment, in either PBS, gargle orsaliva. Bacterial dilutions of 4,800-20,000 in PBS were plated (50microliters), grown at least overnight at 35.5° C., and thebeta-hemolytic colonies counted.

7. Processing the samples involved assaying 0.1 ml of sample in anantigen lateral flow, Rapid Strip Test, for Streptococcus Group A. Teststrips were obtained from McKesson company, USA, and used in accordancewith the manufacture instructions. Estimation of the strength of thepositive line was done visually, by experience lab workers.

Example 1

The following Gargle/Saliva growth Media [GSM] were prepared based onthe Todd Hewitt formula, with successively increasing concentrations ofGlucose, Nitrogen Sources, and Inorganic molecules, as indicated inTable 11 below:

TABLE 11 Nitrogen Inorganic Total Formulation name Glucose Sourcemolecules solids Todd Hewitt Broth X 1 2 g/L 30 g/L 4.9 g/L 37 g/L(TH-1) Todd Hewitt Broth X 2.5 5 g/L 75 g/L 12.25 g/L 92.5 g/L (GSM-1)Todd Hewitt Broth X 4.5 9 g/L 135 g/L 22.05 g/L 166.5 g/L (GSM-2) ToddHewitt Broth X 7 14 g/L 210 g/L 34.3 g/L 259 g/L (GSM-3) Todd HewittBroth X 10 20 g/L 300 g/L 49 g/L 370 g/L (GSM-4)

1.1 ml of each of the above sterile solutions was placed in a tube.

Bacterial suspensions were prepared by spiking even number of bacteriacells in PBS×1, Gargle fluid and saliva.

0.1 ml of bacterial suspension was added to each of the above growthmedia shown in Table 11 and incubated at 35.5° C., in air, for 16.5-17.5hours to obtain cultures.

0.1 ml of each culture was transferred each to a new tube containingSolution A (2M Sodium nitrite) and Solution B (0.2M Acetic acid)followed by a short mix on a Vortex mixer.

McKesson RSTs were dipped into each solution and results were read after5 and 10 minutes according to arbitrary test line intensity scale.Results are presented as the average between the 2 readings.

Results

The following Table 12 summarizes test results, which are reflected aswell in FIG. 28:

TABLE 12 Growth Pure Gargle Saliva Media Test Line intensity TH-1 4.80.4 0.1 GSM-1 4.3 0.5 0.4 GSM-2 4.3 4.3 0.5 GSM-3 0.75 1 1.5 GSM-4 0.50.4 0.3

Conclusions

Both gargle and saliva suspensions grow best in a GSM media having ahigh concentration of solids.

As per the above results, the highest RST readings for gargle suspensiongrowth resulted when GSM-2 was used.

As per the above results, the highest RST readings for saliva suspensiongrowth resulted when GSM-3 was used.

Thus, the inventors have realized that the optimal range of solidsconcentrations in liquid growth media for growing gargle and salivasuspensions should be between 4.5-7×TH, i.e., 4.5-7 times the solidsconcentration in conventional Todd Hewitt liquid growth medium.

In contrast to bacteria sourced from gargle fluid and saliva, the growthof pure GAS culture was inhibited by higher solids concentrations.

Example 2

The following Gargle/Saliva growth Media [SPM] (shown in Table 14 below)were prepared based on a mix of several formulas as indicated in Table13 below with successively increasing concentrations of Glucose,Nitrogen sources, and Inorganic molecules:

TABLE 13 Brain Tryptic Formulation Todd Heart Soy Beef Yeast name HewittInfusion Broth Extract Extract Glucose Percentage 4.44 g/L 6.66 g/L 3.9g/L 10 g/L 3 g/L 2 g/L of total solids for SPM × 1

TABLE 14 Formulation Nitrogen Inorganic Total name Glucose Sourcemolecules solids SPM X 1 2.9 g/L 24.15 g/L 2.9 g/L 30 g/L (SPM-1) SPM X3.5 10.15 85.525 10.15 105 g/L (SPM-3.5 SPM X 4.5 13.05 108.675 13.05135 g/L (SPM-4.5) SPM X 6 17.4 144.9 17.4 180 g/L (SPM-6) SPM X 7 20.3169.05 20.3 210 g/L (SPM-7) SPM X 8.5 24.65 205.275 24.65 255 g/L(SPM-8.5) SPM X 10 29 g/L 241.5 g/L 29 g/L 300 g/L (SPM-10)

1.1 ml of each of the above sterile solutions was placed in a tube.

Bacterial suspensions were prepared by spiking even number of bacteriacells in PBS×1, Gargle fluid and saliva.

0.1 ml of bacterial suspension was added to each of the above growthmedia shown in Table 14 and incubated at 35.5° C., in air, for 22 hoursto obtain cultures.

0.1 ml of each culture was transferred each to a new tube containingSolution A (2M Sodium nitrite) and Solution B (0.2M Acetic acid)followed by a short mix on a Vortex mixer.

McKesson RSTs were dipped into each solution and results were read after5 and 10 minutes according to arbitrary test line intensity scale.Results are presented as the average between the 2 readings.

Results

The following Table 15 summarizes test results, which are reflected aswell in FIG. 29:

TABLE 15 Growth Media Pure Gargle Saliva SPM-1 4.1 1 0.4 SPM-3.5 3.8 0.60.4 SPM-4.5 3.8 1 0.4 SPM-6 4.4 1.6 0.5 SPM-7 1 2.5 1 SPM-8.5 0.5 3 4.4SPM-10 0.5 0.6 0.25

Thus, increasing the solids concentration in SPM growth media has asimilar effect on GAS growth as shown using the GSM media of Example 1.

Solid concentration of growth media has the same effect in both cases(Example 1 and Example 2) regardless of the media nutrient composition.

Example 3

1.1 ml of the TH-1 and 1.1 ml of GSM-1 growth media were each placed inrespective tubes.

Bacterial suspensions were diluted to the final respective cell countsspecified in Table 16 below for both growth media formulas.

0.1 ml of each diluted bacterial suspension was added to a tube of TH-1growth medium and to a tube of GSM-1 growth medium and incubated at35.5° C., in air, for 23 hours, to obtain cultures.

0.1 ml of each culture was each transferred to a new tube containingSolution A (2M Sodium nitrite) and Solution B (0.2M Acetic acid)followed by a short mix on a Vortex mixer.

McKesson RSTs were dipped in the solution and results were read after 5and 10 minutes according to arbitrary test line intensity scale. Resultsare presented as the average between the 2 readings.

Results

Lateral flow values of cultures grown at 35.5° C. for 23h

TABLE 16 CFU per tube Test line intensity Culture CFU per ml TH-1 TH-4.5Pure 180 4.3 4 920 4 3.5 4590 4.6 4.5 45880 4 3.6 458800 4.2 3.9 Gargle180 0.1 4.4 920 1 4.4 4590 2.5 4.3 45880 4 3.4 458800 4.6 2.8

Conclusions

The range of cell numbers per ml in the above experiment represents thevariability of cell counts in gargle fluids that were collected duringclinical study conducted by Hero Scientific.

GAS cells both from pure culture and gargle fluid grow well in TH×4.5and can be easily detected by the RST.

TH×1 is inferior to the high-solids concentration broth when garglefluid is present in the broth at lower cell numbers. At higher cellnumbers, even though TH-1 resulted in higher RST readings, TH-4.5 stillresulted in sufficiently high readings so as to provide unambiguousresults.

In an embodiment, the techniques and apparatus described herein arecombined with techniques and apparatus described in one or more of thefollowing patent applications, which are assigned to the assignee of thepresent application and are incorporated herein by reference:

-   -   International Application PCT/IL2018/050225, filed Feb. 28,        2018, which published as WO 2018/158768 to Fruchter et al.;    -   U.S. Provisional Application 62/727,208, filed Sep. 5, 2018;        and/or    -   an international application filed on even date herein with,        entitled, “Strep testing methods.”

It will be appreciated by persons skilled in the art that the presentinvention is not limited to what has been particularly shown anddescribed hereinabove. Rather, the scope of the present inventionincludes both combinations and subcombinations of the various featuresdescribed hereinabove, as well as variations and modifications thereofthat are not in the prior art, which would occur to persons skilled inthe art upon reading the foregoing description.

1. Apparatus comprising a testing device for testing for the presence ofparticulate in a liquid, the testing device comprising: a liquidcontainer for containing the liquid; a filter, disposed in or downstreamof the liquid container; a liquid-pressure source, which is arranged toapply pressure to drive the liquid contained in the liquid containerthrough the filter; and a filter chamber that is (a) disposed downstreamof the liquid container, (b) shaped so as to define an inlet, and (c) influid communication with the filter.
 2. The apparatus according to claim1, wherein the inlet of the filter chamber has an inlet area that isless than a greatest cross-sectional area of the filter chamber, theinlet area and the greatest cross-sectional area measured in respectiveplanes parallel to each other.
 3. The apparatus according to claim 1,wherein the filter chamber comprises one or more pressure-activatedvalves, not disposed at the inlet of the filter chamber.
 4. Theapparatus according to claim 1, wherein the filter is configured to trapat least 40% of the particulate to be tested and allow passage of theliquid.
 5. The apparatus according to any one of claims 1-4, wherein thefilter is removably disposed upstream of the filter chamber with thefilter partially covering the inlet of the filter chamber.
 6. Theapparatus according to claim 5, wherein the apparatus further comprisesan elongate member configured to push at least a portion of the filterinto the filter chamber.
 7. The apparatus according to claim 5, whereinthe liquid-pressure source comprises a plunger, which comprises aplunger head that is shaped so as to be insertable into the liquidcontainer, and wherein the plunger head is configured to push at least aportion of the filter into the filter chamber.
 8. The apparatusaccording to claim 5, wherein the filter chamber comprises one or morevalves, not disposed at the inlet of the filter chamber.
 9. Theapparatus according to claim 8, wherein the one or more valves compriseone or more pressure-activated valves.
 10. The apparatus according toclaim 9, wherein the one or more valves comprise one or morenon-pressure-activated valves.
 11. The apparatus according to claim 8,wherein the liquid container is shaped so as to define one or moreopenings through a wall of the liquid container, wherein the one or moreopenings are downstream of the filter when the filter is removablydisposed upstream of the filter chamber with the filter partiallycovering the inlet of the filter chamber, and wherein the filter chamberis not disposed so as to receive the liquid that is driven through theone or more openings.
 12. The apparatus according to any one of claims1-4, wherein the apparatus further comprises at least one containercomprising an extraction reagent.
 13. The apparatus according to claim12, wherein the apparatus further comprises a test strip.
 14. A methodcomprising: applying pressure to drive liquid contained in a liquidcontainer of a testing device through a filter of the testing device,wherein the filter is disposed in or downstream of the liquid container,and wherein the liquid includes at least one substance selected from thegroup of substances consisting of gargled fluid, saliva not swabbed froma throat of a patient, and an incubated culture medium containing abiological sample; and thereafter, testing, within a filter chamber ofthe testing device, for the presence of particulate trapped by thefilter while the filter is disposed at least partially in the filterchamber, wherein the filter chamber is (a) disposed downstream of theliquid container, (b) shaped so as to define an inlet, and (c) in fluidcommunication with the filter.
 15. The method according to claim 14,wherein testing comprises applying an extraction reagent to the filterwhile the filter is in the filter chamber.
 16. The method according toclaim 14, wherein applying the pressure comprises applying positivepressure using a positive-pressure pump disposed upstream of the filter.17. A method comprising: applying pressure to drive liquid contained ina liquid container of a testing device (a) through a filter of thetesting device and (b) then through one or more valves of the testingdevice, wherein the filter is disposed in or downstream of the liquidcontainer, wherein the one or more valves are disposed downstream of thefilter, and wherein the liquid includes at least one substance selectedfrom the group of substances consisting of gargled fluid, saliva notswabbed from a throat of a patient, and an incubated culture mediumcontaining a biological sample; and thereafter, testing, within thetesting device, for the presence of particulate trapped by the filterwhile the one or more valves are closed and the filter is disposed inthe testing device.
 18. The method according to claim 17, whereintesting comprises applying an extraction reagent to the filter.
 19. Themethod according to claim 18, wherein testing further comprises afterapplying the extraction reagent, inserting a test strip into the testingdevice and examining the test strip to test for the presence of theparticulate.
 20. The method according to claim 17, wherein the liquidincludes the saliva not swabbed from the throat of the patient.
 21. Themethod according to claim 17, wherein the one or more valves include oneor more pressure-activated valves.
 22. The method according to claim 17,wherein the one or more valves include one or morenon-pressure-activated valves.
 23. The method according to claim 22,wherein the testing device is configured to automatically close the oneor more non-pressure-activated valves after the pressure is applied todrive the liquid through the filter and then through the one or morenon-pressure-activated valves.
 24. The method according to claim 22,wherein the one or more non-pressure-activated valves include two discsthat are shaped so as to define respective sets of openings, and whereinthe one or more non-pressure-activated valves are configured to assumeopen and closed states when the two sets of openings are aligned andnon-aligned with each other.
 25. The method according to claim 22,wherein applying the pressure comprises pushing a plunger including aplunger head inserted into the liquid container, and wherein the testingdevice is configured to automatically close the one or morenon-pressure-activated valves after the plunger applies the pressure todrive the liquid contained in the liquid container through the filterand then through the one or more non-pressure-activated valves.
 26. Themethod according to claim 25, wherein the testing device is configuredsuch that motion of the plunger automatically closes the one or morenon-pressure-activated valves after the plunger applies the pressure todrive the liquid contained in the liquid container through the filterand then through the one or more non-pressure-activated valves.
 27. Themethod according to claim 26, wherein pushing the plunger compriserotating the plunger, and wherein the testing device is configured suchthat rotational motion of the plunger automatically closes the one ormore non-pressure-activated valves after the plunger applies thepressure to drive the liquid contained in the liquid container throughthe filter and then through the one or more non-pressure-activatedvalves.
 28. The method according to claim 27, wherein the plunger isshaped so as to define one or more plunger threads, and wherein aninternal wall of the liquid container is shaped so as to define one ormore liquid-container threads that engage the one or more plungerthreads such that rotation of the plunger advances the plunger in adownstream direction within the liquid container.
 29. The methodaccording to claim 27, wherein the one or more non-pressure-activatedvalves comprise two discs that are shaped so as to define respectivesets of openings, and wherein the one or more non-pressure-activatedvalves are configured to assume open and closed states when the two setsof openings are aligned and non-aligned with each other, wherein pushingthe plunger comprise rotating the plunger, and wherein the testingdevice is configured such that rotational motion of the plungerautomatically closes the one or more non-pressure-activated valves byrotating at least one of the two discs with respect to the other of thediscs, after the plunger applies the pressure to drive the liquidcontained in the liquid container through the filter and then throughthe one or more non-pressure-activated valves.
 30. The method accordingto claim 17, wherein the testing device further includes a filterchamber that is (a) disposed downstream of the liquid container, (b)shaped so as to define an inlet, and (c) in fluid communication withfilter.
 31. The method according to claim 30, wherein the filter chamberincludes at least one of the one or more valves, not disposed at theinlet of the filter chamber.
 32. The method according to claim 30,wherein applying the pressure comprises applying the pressure while thefilter is removably disposed upstream of the filter chamber with thefilter partially covering the inlet of the filter chamber.
 33. Themethod according to claim 32, wherein the method further comprises,after applying the pressure and before testing for the presence of theparticulate trapped by the filter, pushing at least a portion of thefilter into the filter chamber.
 34. The method according to claim 30,wherein the filter chamber includes at least one of the one or morevalves, not disposed at the inlet of the filter chamber.
 35. The methodaccording to claim 34, wherein the liquid container is shaped so as todefine one or more openings through a wall of the liquid container,wherein the one or more openings are downstream of the filter when thefilter is removably disposed upstream of the filter chamber with thefilter partially covering the inlet of the filter chamber, wherein thefilter chamber is not disposed so as to receive the liquid that isdriven through the one or more openings, and wherein applying thepressure comprises applying the pressure to drive the liquid (i)partially through (a) the filter and (b) one or more of the one or morevalves of the testing device and (ii) partially through the one or moreopenings.
 36. The method according to claim 17, wherein the filter isconfigured to trap at least 40% of the particulate.
 37. The methodaccording to claim 17, wherein the particulate comprises biologicalparticulate.
 38. The method according to claim 37, wherein thebiological particulate is selected from the group consisting of: amicroorganism, a fungus, a bacterium, a spore, a virus, a mite, abiological cell, a biological antigen, a protein, a protein antigen, anda carbohydrate antigen.
 39. The method according to claim 17, whereintesting for the presence of the particulate comprises applying anextraction reagent to the filter after applying the pressure.
 40. Themethod according to claim 39, wherein testing for the presence of theparticulate comprises using a test strip.
 41. Apparatus comprising atesting device for testing for the presence of particulate in a liquid,the testing device comprising: a liquid container for containing theliquid, the liquid container shaped so as to define upstream anddownstream openings; a filter, removably disposed in the liquidcontainer; and a plunger head that (a) is shaped so as to be insertableinto the liquid container so as to form a movable seal with a wall ofthe liquid container, and (b) is arranged such that when pushed, theplunger head applies pressure to drive the liquid contained in theliquid container through the filter and then through the downstreamopening, wherein the testing device is configured such that rotation ofthe plunger head radially compresses the filter toward a centrallongitudinal axis of the plunger head.
 42. The apparatus according toclaim 41, wherein the testing device is configured such that therotation of the plunger head crushes the filter.
 43. A methodcomprising: inserting a plunger head into a liquid container of atesting device so as to form a movable seal with a wall of the liquidcontainer; pushing the plunger head to apply pressure to drive liquidcontained in the liquid container through a filter of the testing deviceand then through a downstream opening of the liquid container, whichalso has an upstream opening, wherein the filter is removably disposedin the liquid container; and rotating the plunger head to radially crushthe filter toward a central longitudinal axis of the plunger head. 44.The method according to claim 43, further comprising, after rotating theplunger head, testing the filter for the presence of particulate trappedby the filter.
 45. The method according to claim 43, wherein rotatingthe plunger head crushes the filter.
 46. The method according to claim45, wherein the plunger head includes a protrusion, and wherein rotatingthe plunger head causes the protrusion to move radially toward thecentral longitudinal axis of the plunger head.
 47. Apparatus comprisinga testing device for testing for the presence of particulate in aliquid, the testing device comprising: a liquid container for containingthe liquid, wherein the liquid container has an internal volume ofbetween 0.5 and 500 ml; one or more valves; a filter, disposed in ordownstream of the liquid container and upstream of the one or morevalves; and a plunger, which (a) comprises a plunger head that is shapedso as to be insertable into the liquid container, and (b) is arranged toapply pressure to drive the liquid contained in the liquid containerthrough the filter and then through the one or more valves.
 48. Theapparatus according to claim 47, wherein the one or more valves compriseone or more pressure-activated valves.
 49. The apparatus according toclaim 47, wherein the one or more valves comprise one or morenon-pressure-activated valves.
 50. The apparatus according to claim 49,wherein the one or more non-pressure-activated valves comprise two discsthat are shaped so as to define respective sets of openings, and whereinthe one or more non-pressure-activated valves are configured to assumeopen and closed states when the two sets of openings are aligned andnon-aligned with each other.
 51. The apparatus according to claim 49,wherein the testing device is configured to automatically close the oneor more non-pressure-activated valves after the plunger applies thepressure to drive the liquid contained in the liquid container throughthe filter and then through the one or more non-pressure-activatedvalves.
 52. The apparatus according to claim 51, wherein the testingdevice is configured such that motion of the plunger automaticallycloses the one or more non-pressure-activated valves after the plungerapplies the pressure to drive the liquid contained in the liquidcontainer through the filter and then through the one or morenon-pressure-activated valves.
 53. The apparatus according to claim 52,wherein the testing device is configured such that rotational motion ofthe plunger automatically closes the one or more non-pressure-activatedvalves after the plunger applies the pressure to drive the liquidcontained in the liquid container through the filter and then throughthe one or more non-pressure-activated valves.
 54. The apparatusaccording to claim 53, wherein the plunger is shaped so as to define oneor more plunger threads, and wherein an internal wall of the liquidcontainer is shaped so as to define one or more liquid-container threadsthat engage the one or more plunger threads such that rotation of theplunger advances the plunger in a downstream direction within the liquidcontainer.
 55. The apparatus according to claim 53, wherein the one ormore non-pressure-activated valves comprise two discs that are shaped soas to define respective sets of openings, and wherein the one or morenon-pressure-activated valves are configured to assume open and closedstates when the two sets of openings are aligned and non-aligned witheach other, and wherein the testing device is configured such thatrotational motion of the plunger automatically closes the one or morenon-pressure-activated valves by rotating at least one of the two discswith respect to the other of the discs, after the plunger applies thepressure to drive the liquid contained in the liquid container throughthe filter and then through the one or more non-pressure-activatedvalves.
 56. The apparatus according to claim 47, wherein the filter hasa filter surface area of an upstream side of the filter that equalsbetween 0.3 and 100 cm2.
 57. The apparatus according to claim 56,wherein the filter surface area equals between 0.3 and 30 cm2.
 58. Theapparatus according to claim 47, wherein the filter is configured totrap at least 40% of the particulate to be tested and allow passage ofthe liquid.
 59. The apparatus according to any one of claims 47-58,wherein the testing device further comprises a filter chamber that is(a) disposed downstream of the liquid container, (b) shaped so as todefine an inlet, and (c) in fluid communication with the filter.
 60. Theapparatus according to claim 59, wherein the filter chamber comprises atleast one of the one or more valves, not disposed at the inlet of thefilter chamber.
 61. The apparatus according to claim 59, wherein thefilter is removably disposed upstream of the filter chamber with thefilter partially covering the inlet of the filter chamber.
 62. Theapparatus according to claim 61, wherein the testing device furthercomprises a support for the filter, disposed at least partially betweenthe inlet of the filter chamber and the filter.
 63. The apparatusaccording to claim 61, wherein the apparatus further comprises anelongate member configured to push at least a portion of the filter intothe filter chamber.
 64. The apparatus according to any one of claims47-58, wherein the one or more valves are one or more first valves, andwherein the testing device further comprises one or more second pressurerelief valves, which are in fluid communication with the liquidcontainer and are disposed upstream of the filter.
 65. The apparatusaccording to any one of claims 47-58, wherein the apparatus furthercomprises at least one container containing an extraction reagent. 66.The apparatus according to claim 65, wherein the apparatus furthercomprises a test strip.
 67. Apparatus comprising a testing device fortesting for the presence of particulate in a liquid, the testing devicecomprising: a liquid container for containing the liquid, wherein theliquid container has an internal volume of between 0.5 and 500 ml; oneor more non-pressure-activated valves; a filter, disposed in ordownstream of the liquid container and upstream of the one or morevalves; and a liquid-pressure source, which is arranged to applypressure to drive the liquid contained in the liquid container throughthe filter and then through the one or more valves, wherein the testingdevice is configured to automatically close the one or morenon-pressure-activated valves after the liquid-pressure source appliesthe pressure to drive the liquid contained in the liquid containerthrough the filter and then through the one or morenon-pressure-activated valves.
 68. The apparatus according to claim 67,wherein the testing device is configured such that motion of theliquid-pressure source automatically closes the one or morenon-pressure-activated valves after the liquid-pressure source appliesthe pressure to drive the liquid contained in the liquid containerthrough the filter and then through the one or morenon-pressure-activated valves.
 69. The apparatus according to claim 68,wherein the testing device is configured such that rotational motion ofthe liquid-pressure source automatically closes the one or morenon-pressure-activated valves after the liquid-pressure source appliesthe pressure to drive the liquid contained in the liquid containerthrough the filter and then through the one or morenon-pressure-activated valves.
 70. The apparatus according to claim 69,wherein the one or more non-pressure-activated valves comprise two discsthat are shaped so as to define respective sets of openings, and whereinthe one or more non-pressure-activated valves are configured to assumeopen and closed states when the two sets of openings are aligned andnon-aligned with each other, and wherein the testing device isconfigured such that rotational motion of the liquid-pressure sourceautomatically closes the one or more non-pressure-activated valves byrotating at least one of the two discs with respect to the other of thediscs, after the liquid-pressure source applies the pressure to drivethe liquid contained in the liquid container through the filter and thenthrough the one or more non-pressure-activated valves.
 71. A methodcomprising: incubating gargled fluid for between 12 and 75 hours in acontainer that contains a liquid growth medium, a dehydrated growthmedium, or a gel growth medium; and thereafter, performing a strep testusing a rapid strep test (RST) technique on the gargled fluid and growthmedium.
 72. The method according to claim 71, wherein performing thestrep test using the RST technique comprises performing a lateral flowtest.
 73. The method according to claim 71, wherein performing the streptest using the RST technique comprises performing an RST techniqueselected from the group consisting of: an ELISA-based RST, anantibody-coated-beads-based RST, a nucleic-acid-based RST, and afluorescent immunoassaying (FIA) RST.
 74. The method according to claim71, wherein performing the strep test using the RST technique furthercomprises filtering the gargled fluid and the growth medium afterincubating, and performing the strep test using the RST technique on thefilter.
 75. The method according to claim 74, wherein filtering thegargled fluid and the growth medium after incubating comprises: placingthe gargled fluid and the growth medium in a liquid container of atesting device; and applying pressure to drive the gargled fluid and thegrowth medium contained in the liquid container (a) through a filter ofthe testing device and (b) then through one or more valves of thetesting device, wherein the filter is disposed in or downstream of theliquid container, and wherein the one or more valves are disposeddownstream of the filter.
 76. A method for testing for the presence ofparticulate in gargled fluid, the method comprising: incubating thegargled fluid for between 12 and 75 hours in a container that contains aliquid growth medium, a dehydrated growth medium, or a gel growthmedium; and thereafter, performing a test for the particulate using arapid test technique on the gargled fluid and growth medium.
 77. Themethod according to claim 76, wherein performing the test using therapid test technique comprises performing a lateral flow test.
 78. Themethod according to claim 76, wherein performing the test using therapid test technique comprises performing a rapid test techniqueselected from the group consisting of: an ELISA-based rapid test, anantibody-coated-beads-based rapid test, a nucleic-acid-based rapid test,and a fluorescent immunoassaying (FIA) rapid test.
 79. A method fortesting for the presence of particulate in gargled fluid, the methodcomprising: incubating the gargled fluid for between 12 and 75 hours ina container that contains a liquid growth medium, a dehydrated growthmedium, or a gel growth medium; and thereafter, performing a lateralflow test for the particulate on the gargled fluid and growth medium.80. The method according to claim 79, wherein the particulate is strep,and wherein performing the lateral flow test comprises performing thelateral flow test for the strep.
 81. The method according to any one ofclaims 71, 76, and 79, wherein the container does not contain agar. 82.A method comprising: incubating saliva not swabbed from a patient'sthroat for between 12 and 75 hours in a container that contains a liquidgrowth medium, a dehydrated growth medium, or a gel growth medium; andthereafter, performing a strep test using a rapid strep test (RST)technique on the saliva and growth medium.
 83. The method according toclaim 82, wherein the saliva not swabbed from the throat of the patientis saliva spit by the patient.
 84. The method according to claim 82,further comprising mixing the saliva with the growth medium beforeincubating.
 85. The method according to claim 82, wherein performing thestrep test using the RST technique comprises performing a lateral flowtest.
 86. The method according to claim 82, wherein performing the streptest using the RST technique comprises performing an RST techniqueselected from the group consisting of: an ELISA-based RST, anantibody-coated-beads-based RST, a nucleic-acid-based RST, and afluorescent immunoassaying (FIA) RST.
 87. The method according to claim82, wherein incubating comprises: receiving, on an absorbent element,saliva from the patient's mouth; and thereafter, placing the absorbentelement into the container that contains the liquid growth medium,dehydrated growth medium, or gel growth medium.
 88. The method accordingto claim 87, wherein performing the strep test using the RST techniquecomprises performing the RST technique on the saliva and the growthmedium while the saliva and the growth medium are in the container. 89.Apparatus comprising A testing kit for testing for the presence ofparticulate in a liquid, the testing kit comprising: a liquid containerfor containing the liquid, the liquid container shaped so as to defineupstream and downstream openings; a filter, disposed in or downstream ofthe liquid container; and a plunger head that (a) is shaped so as to beinsertable into the liquid container so as to form a movable seal with awall of the liquid container, and (b) is arranged such that when pushed,the plunger head applies pressure to drive the liquid contained in theliquid container through the filter and then through the downstreamopening, wherein the testing kit does not comprise a plunger shaft. 90.The apparatus according to claim 89, wherein the filter is configured totrap at least 40% of a particulate to be tested and allow passage of theliquid.
 91. The apparatus according to claim 89, further comprisingsterile packaging, in which at least the liquid container, plunger head,and the filter are removably disposed.
 92. The apparatus according toclaim 89, wherein the liquid container comprises a liquid-tight sealdisposed downstream of the filter, and wherein the testing kit isarranged such that when the plunger head is pushed, the plunger headapplies the pressure to break or open the seal and drive the liquidthrough the filter and then through the downstream opening.
 93. A methodcomprising: receiving a testing kit including (a) a liquid container,the liquid container shaped so as to define upstream and downstreamopenings, (b) a filter, disposed in or downstream of the liquidcontainer, (c) and a plunger head; coupling the plunger head to aplunger shaft; receiving a liquid in the liquid container; inserting theplunger head into the liquid container so as to form a movable seal witha wall of the liquid container; and using the plunger shaft, pushing theplunger head to apply pressure to drive the liquid contained in theliquid container through the filter and then through the downstreamopening, wherein the testing kit does not include the plunger shaft. 94.The method according to claim 93, further comprising, after pushing theplunger head, testing for the presence of particulate trapped by thefilter.